Life-course publications map

Publications from the LongITools project are mapped against the life-course below. The coloured bars on the timeline show the ages of the people studied. The categories are either exposures, molecular responses or outcomes of the study. Some publications cannot be mapped against the life-course and are listed in a table below the map (keep scrolling!).

For SPOTLIGHT publications, please visit the resources page for a summary of the key findings.

Publications Map © Beta Technology Ltd 2020

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SPOTLIGHT: Residential Exposure to Traffic Noise and Incidence of Depression and Anxiety from Childhood Through Adulthood: A Finnish Register Study (August 2025)

05/08/2025 - Yiyan He et al. Environmental Research. LongITools authors: Yiyan He, Jules Kerckhoffs, Sylvain Sebert, Anna Pulakka - University of Oulu, Utrecht University

Environmental noise caused by various sources, including road, rail, and airport traffic and construction, is the second biggest environmental health concern in Europe. Noise may affect human health through both direct and indirect pathways. High noise levels, via direct pathway, damage the auditory system and disrupt sleep. The indirect pathway also involves sleep disturbance and additional cognitive and emotional responses, contributing to cardiovascular and neurological diseases. Recent evidence shows associations with mental disorders. However, the quality of available research evidence remains low. In this study, we found that exposure to road noise above 53 dB (Lden), as the WHO recommended noise threshold, is associated with the risk of depression and anxiety in the young population.

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Identifying key predictors of mid-childhood obesity in a population-based cohort study: An evidence synthesis and predictive modeling study (June 2025)

12/06/2025 - Yuchan Mou et al. Obesity Reviews. LongITools authors: Vincent Jaddoe, Janine Felix - Erasmus MC
Cohort(s): Generation R

A wide spectrum of predictors of childhood overweight and obesity has been identified over past decades, yet a quantitative overview of multidisciplinary predictors is missing, and the relative importance and their collective contribution to childhood obesity remains unclear. In this study, researchers found that mid-childhood BMI and weight status were associated with multiple predictors, particularly those related to preconception and prenatal parental health, early-life weight, and child behaviours.

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Prenatal Smoking Exposures and Epigenome-wide Methylation in Newborn Blood (June 2025)

06/06/2025 - Thanh T. Hoang et al. Environmental Health Perspectives. LongITools authors: Vincent Jaddoe, Janine Felix - Erasmus MC

Maternal sustained smoking during pregnancy is associated with thousands of differentially methylated CpGs in newborns, but impacts of other prenatal tobacco smoking exposures remain unclear. Researchers conducted a large meta-analysis of prenatal tobacco smoking exposures and epigenome-wide newborn blood DNA methylation through the Pregnancy And Childhood Epigenetics Consortium (PACE). They found maternal sustained smoking has the largest impact on newborn DNA methylation, suggesting a strong influence of the intrauterine environment. Minimal impacts were observed for less studied exposures including SHS, maternal former smoking and paternal smoking.

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Determinants of body mass index in early life: findings from an exposome-wide assocation study with follow-up replication and mendelian randomization analyses (May 25)

02/05/2025 - Jie V Zhao et al. Exposome. LongITools authors: Ana Goncalves Soares, Tim Cadman, Barbara Heude, Vincent Jaddoe, Justiina Ronkainen, Sylvain Sebert, Morris Swertz, Wen Lun Yuan, Ahmed Elhakeem - University of Bristol, University Medical Center Groningen, National Institute of Medical Research, Erasmus MC, University of Oulu
Cohort(s): ALSPAC

Studies of factors influencing body mass index (BMI) mostly focus on hypothesized/established factors. We explored potential factors influencing BMI across childhood and adolescence using an association study without imposing any hypothesis (hypothesis-free exposome-wide, ExWAS). We also aimed to provide an external replication and Mendelian randomization (MR), a method that, using genetic information, can be used to determine whether a certain exposure can causes a specific health outcome, such as BMI. Our results suggests that more TV viewing time in early-childhood could increase BMI in mid-childhood.

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SPOTLIGHT: The Adverse Influence of Maternal Glycaemia During Pregnancy on Offspring’s Cardiometabolic Health Profiles (April 2025)

23/04/2025 - Wenlun Yuan et al. Acta Paediatrica. LongITools authors: Wenlun Yuan, Marie Aline Charles, Barbara Heude - National Institute of Medical Research
Cohort(s): EDEN

Using data from EDEN French birth cohort study, four cardiometabolic risk profiles were identified in girls and boys at age 5–6 years. Maternal hyperglycaemia appeared to have only a marginal influence on them, possibly due to strict glycaemic control following the GDM diagnosis.

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SPOTLIGHT: Exposure to fine particulate matter (PM2.5) in adults is associated with immune cell gene expression related to inflammation, the electron transport chain and cell cycle regulation (April 25)

23/05/2025 - Amanda Rundblad et al. Environmental Epigenetics. LongITools authors: Amanda Rundblad, Siddhartha Das, Gina Ginos, Jason Matthews, Kirsten Holven, Stine Marie Ulven - University of Oslo, Erasmus MC

Exposure to air pollution and an unhealthy built environment increase disease risk by impacting metabolic risk factors and inflammation, potentially via epigenetic modifications and effects on gene expression. In this study, we aimed to explore associations between fine particulate matter (PM2.5), black carbon, ozone, nitrogen dioxide, distance to nearest water body, normalized difference vegetation index, and impervious surface and gene expression profiles in adults.In conclusion, PM2.5 is strongly associated with various gene expression profiles, which provide information about the underlying mechanisms of the detrimental health effects of exposure to PM2.5.

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SPOTLIGHT: Timing based clustering of childhood BMI trajectories reveals differential maturational patterns; Study in the Northern Finland Birth Cohorts 1966 and 1986 (January 2025)

22/02/2025 - Anni Heiskala et al. International Journal of Obesity. LongITools authors: Anni Heiskala, Rozenn Nedelec, Justiina Ronkainen, Marjo-Riitta Järvelin, Sylvain Sebert - University of Oulu, Imperial College London
Cohort(s): Northern Finland Birth Cohorts 1966 and 1986

Children’s biological age does not always correspond to their chronological age. Although childhood BMI trajectories follow a recognisable pattern, there is variation in the timing of the pattern between children that could refer to the maturational differences between children. We identified three clusters with different patterns of childhood BMI trajectories in regarding timing. Findings highlight that the mismatch between chronological and maturational age deserves further attention in the context of BMI in children.

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Associations of maternal night shift work during pregnancy with DNA methylation in offspring: A meta-analysis in the PACE Consortium (January 2025)

22/01/2025 - Irene Marques et al. Clinical Epigenetics. LongITools authors: Irene Marques, Janine Felix - Erasmus MC

Over 20% of the European workforce engages in shift work. Women exposed to shift work during pregnancy have an increased risk of pregnancy-related complications, but the underlying biologic mechanisms are not well understood. In this study, researchers found that maternal night shift work during pregnancy was associated with newborn DNA methylation at 3 CpGs. This work strengthens evidence that DNA methylation could be a marker or mediator of the impacts of circadian rhythm disturbances during pregnancy on child cardiovascular health.

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A meta-analysis of epigenome-wide association study of ultra-processed food consumption with DNA methylation in European children (January 2025)

07/01/2025 - Joana Llauradó-Pont et al. Clinical Epigenetics. LongITools authors: Janine Felix, Vincent Jaddoe - Erasmus MC

There is limited knowledge on how diet affects the epigenetic landscape in children. Ultra-processed food consumption is emerging as an important factor impacting health, but mechanisms need to be uncovered. We therefore aimed to assess the association between ultra-processed food consumption and DNA methylation in children. This study shows that there may be some impact of the presence of ultra-processed food in the diet on DNA methylation, but this might not be a key mechanism underlying the health effects of ultra-processed food in children.

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Association of exposure to second-hand smoke during childhood with blood DNA methylation (January 2025)

02/01/2025 - Marta Cosin-Tomas et al. Environment International. LongITools authors: Vincent Jaddoe and Janine Felix. - Erasmus MC

By recent estimates, 40% of children worldwide are exposed to second-hand smoke (SHS), which has been associated with adverse health outcomes. While numerous studies have linked maternal smoking during pregnancy (MSDP) to widespread differences in child blood DNA methylation (DNAm), research specifically examining postnatal SHS exposure remains sparse. To address this gap, researchers conducted epigenome-wide meta-analyses to identify associations of postnatal SHS and child blood DNAm. The study included six cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium and highlights the potential biological effects of second- hand smoking during childhood on blood DNA methylation.

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SPOTLIGHT: Long-term air pollution exposure and the blood metabolome: The Rotterdam Study (December 2024)

15/12/2024 - Bigina N.R. Ginos. Environmental Research. LongITools authors: Gina Ginos - Erasmus MC
Cohort(s): Rotterdam Study

Air pollution is a well-established risk factor for several adverse health outcomes, but the specific molecular mechanisms, particularly those involving metabolic processes, remain incompletely understood. The study revealed associations of long-term air pollutant exposure with several metabolites and enrichment of two pathways, which are known to be involved in the adrenal and reproductive system and cell metabolism. This research adds new knowledge about the biological pathways potentially linking air pollution to chronic diseases and also emphasises the need for more research on how air pollution affects vulnerable groups, such as the elderly.

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SPOTLIGHT: Air pollution exposure is associated with gene expression in children (December 2024)

08/01/2025 - Siddhartha Das et al. Environmental Epigenetics. LongITools authors: Siddhartha Das, Amanda Rundblad, Irene Fontes Marques, Ana Goncalves Soares, Vincent Jaddoe, Jason Matthews, Kirsten Holven, Nicholas Timpson, Janine Felix, Stine Marie Ulven - University of Oslo, Erasmus MC, University of Bristol
Cohort(s): Generation R, ALSPAC

In this paper we aimed to study the associations between environmental exposures, including particulate matter less than 2.5uM or 10uM (PM2.5 or PM10), nitrogen dioxide as well as natural spaces, and gene expression in children. Among the environmental exposure, PM2.5 exposure was associated with the largest number of genes, and most of the genes were negatively associated. The associated genes enriched for innate immune response pathways including interferon alpha and gamma response that are involved in response to bacterial and viral infection. Hence, our research suggests that exposure to PM2.5 in early life may compromise the immune system response against microbial infection and this could have adverse implications in later life.

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SPOTLIGHT: Examining associations of air pollution and green space with depressive symptoms in adults: A LongITools cross-cohort analysis (November 2024)

18/11/2024 - Irina Motoc et al. Environmental Research. LongITools authors: Irina Motoc, Gina Ginos, Ana Goncalves Soares, Ahmed Elhakeem, Maryam Kavousi, Tessa Roseboom, Susanne de Rooij - Amsterdam University Medical Centers, location AMC, Erasmus MC, University of Bristol
Cohort(s): Dutch Famine Birth Cohort, Rotterdam Study, ALSPAC

Associations between exposure to air pollution and green environments and trajectories of depressive symptoms over time was examined in four population-based cohorts in the UK and the Netherlands. Although the environmental variables did not seem to be related to the trajectories of depressive symptoms, higher air pollution was associated with more depressive symptoms in two cohorts and more green exposure was associated with fewer depressive symptoms in one cohort.

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Cesarean delivery and blood DNA methylation at birth and childhood: Meta-analysis in the Pregnancy and Childhood Epigenetics Consortium (November 2024)

27/11/2024 - Siwen Wang et al. Science Advances. LongITools authors: Barbara Heude, Janine Felix - Erasmus MC, National Institute of Medical Research

Children born via caesarean delivery have a higher risk of metabolic, immunological, and neurodevelopmental disorders compared to those born via vaginal delivery, although mechanisms remain unclear. Researchers identified six methylation sites in cord blood associated with caesarean delivery. None of these methylation sites were associated with caesarean delivery in childhood, and no additional methylation sites were identified in childhood. Further research is needed to elucidate caesarean delivery’s molecular influence on offspring health.

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A framework for conducting GWAS using repeated measures data with an application to childhood BMI (November 2024)

20/11/2024 - Kimberley Burrows et al. Nature Communications. LongITools authors: Anni Heiskala, Zhanna Balkhiyarova, Marjo-Riitta Järvelin, Inga Prokopenko, Sylvain Sebert - University of Oulu, University of Surrey, Imperial College London

This study presents a novel framework for conducting genome-wide association studies (GWAS) that accounts for changes in human traits over time. By focusing on childhood body mass index (BMI), the research highlights the potential of this framework to uncover genetic effects that vary with age, providing insights into the biological mechanisms influencing trait development and its health implications.

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Mapping prenatal predictors and neurobehavioral outcomes of an epigenetic marker of neonatal inflammation – A longitudinal population-based study (November 2024)

01/11/2024 - Anna Suleri et al. Brain, Behavior, and Immunity. LongITools authors: Janine Felix - Erasmus MC
Cohort(s): Generation R

A DNA methylation profile score at birth may be used as a marker of sustained inflammation (MPS-CRP) in neonates. Little is known about predictors for − and offspring outcomes of − MPS-CRP in the general population. In this study, MPS-CRP at birth was linked to prenatal lifestyle factors but not to maternal medical conditions, or child genetic factors. MPS-CRP at birth was associated with child white matter alterations over time, but not with psychiatric symptoms. The use of DNA methylation as a marker of neonatal inflammation should be further examined using a wider range of immune markers.

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Women exposed to famine in early gestation have increased mortality up to age 76 years (October 2024)

01/10/2024 - Aline Marileen Wiegersma et al. Paediatric and Perinatal Epidemiology. LongITools authors: Tessa Roseboom, Susanne de Rooij - Amsterdam University Medical Centers, location AMC
Cohort(s): Dutch Famine Birth Cohort

The nutritional environment in early life may have long lasting effects on health and mortality. This study showed that women, but not men, who were exposed to famine during early gestation had increased mortality up to the age of 76 years compared to those unexposed.

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Epigenome-wide meta-analysis of prenatal vitamin D insufficiency and cord blood DNA methylation (October 2024)

17/10/2024 - Elizabeth W. Deimer et al. Epigenetics. LongITools authors: Janine Felix - Erasmus MC

Low maternal vitamin D concentrations during pregnancy have been associated with a range of offspring health outcomes. DNA methylation is one mechanism by which the maternal vitamin D status during pregnancy could impact offspring’s health in later life. In this study, researchers in the PACE consortium aimed to evaluate whether maternal vitamin D insufficiency during pregnancy was associated with DNA methylation in the offspring cord blood. They did not find convincing evidence of an association of vitamin D insufficiency with offspring DNA methylation.

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Prenatal exposure to common infections and newborn DNA methylation: A prospective, population-based study (October 2024)

21/10/2024 - Anna Suleri et al. Brain, Behavior, and Immunity. LongITools authors: Janine Felix - Erasmus MC

Previous studies reported DNA methylation differences in children exposed to severe infections in utero. However, we do not find evidence for associations of common infections during pregnancy with DNA methylation or epigenetic (“biological”) ageing in cord blood.

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Prenatal exposure to undernutrition is associated with a specific lipid profile predicting future brain aging (September 2024)

30/09/2024 - Stuart G. Snowden et al. npj Aging. LongITools authors: Tessa Roseboom, Susanne de Rooij - Amsterdam University Medical Centers, location AMC
Cohort(s): Dutch Famine Birth Cohort

The nutritional environment in early life may affect cardiovascular health as well as cognitive and brain aging. In this study, researchers showed that prenatal undernutrition was associated with an altered lipid profile predictive of BrainAGE 10 years later.

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Evaluation and comparison of nine growth and development-based measures of pubertal timing (August 2024)

11/04/2025 - Ahmed Elhakeem et al. Communications Medicine. LongITools authors: Ahmed Elhakeem, Ana Goncalves Soares, Sylvain Sebert, Nicholas Timpson - University of Bristol, University of Oulu
Cohort(s): ALSPAC

Age of puberty varies between individuals and can affect a person’s future health. There are many different indicators of pubertal timing, and how they relate to each other is unclear. The aim of this study was to quantitatively compare nine indicators of pubertal timing. The findings provide insights into the measurements of the timing of pubertal growth and development and illustrate the value of various pubertal timing indicators in life-course research.

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SPOTLIGHT: Sex and population differences in the cardiometabolic continuum: a machine learning study using the UK Biobank and ELSA-Brasil cohorts (August 2024)

30/08/2024 - Daniela Polessa Paula. BMC Public Health. LongITools authors: Daniela Paula, Marina Camacho, Karim Lekadir - University of Barcelona

This study identifies five distinct patterns of cardiometabolic disease progression using machine learning, revealing significant sex and country differences in disease onset and prevalence. Findings highlight the need for targeted public health interventions, especially for women, to address the varied impacts of cardiometabolic diseases across different populations.

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Green spaces and respiratory, cardiometabolic, and neurodevelopmental outcomes: An individual-participant data meta-analysis of >35.000 European children (August 2024)

01/08/2024 - Amanda Fernandes et al. Environment International. LongITools authors: Ahmed Elhakeem, Barbara Heude, Vincent Jaddoe - University of Bristol, National Institute of Medical Research, Erasmus MC

This is the first meta-analysis study to explore the exposure to green spaces during pregnancy and childhood on various health outcomes in children of multiple European countries. The results showed that living in greener areas during childhood was associated with better lung function in school-age children. Our findings highlight the importance of integrating green spaces into urban environments for better respiratory health, also in children. If the way cities are configured is a factor that contributes to inequality, urban planning that consciously contributes to alleviating inequity is important.

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SPOTLIGHT: Eight-year diet and physical activity intervention affects serum metabolites during childhood and adolescence: A nonrandomized controlled trial (July 2024)

30/07/2024 - Iman Zarei et al. iScience. LongITools authors: Iman Zarei, Santtu Mikkonen, Marjukka Kolehmainen, Kati Hanhineva, Timo A. Lakka - University of Eastern Finland

The study shows that long-term lifestyle interventions in childhood and adolescence can significantly improve cardiometabolic health. This improvement is linked to specific changes in serum metabolites, particularly fatty amides and microbiota-derived metabolites. The study highlights that early interventions can curb metabolic risks and prevent cardiometabolic diseases by tracking these changes over an 8-year period. Understanding these metabolic alterations provides valuable insights into preventing cardiometabolic and other non-communicable diseases from an early age.

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SPOTLIGHT: Longitudinal associations of an exposome score with serum metabolites from childhood to adolescence (July 2024)

20/09/2024 - Darren Healy et al. Communications Biology. LongITools authors: Darren Healy, Iman Zarei, Santtu Mikkonen, Kati Hanhineva, Marjukka Kolehmainen and Timo Lakka - University of Eastern Finland

In this study, a higher exposome score, indicating unhealthier environmental exposures and lifestyle habits, was associated with altered serum levels of 31 metabolites measured by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) in childhood and adolescence. These metabolites were predominantly phospholipids, fatty acids, amino acids, xenobiotics, and energy-related metabolites – in previous studies, some of these metabolites have been linked to the development of, for example, obesity, type 2 diabetes, or cardiovascular diseases in later life.

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Epigenetic signature of very low birth weight in young adult life (June 2024)

19/06/2024 - Juho Kuula et al. Pediatric Research. LongITools authors: Justiina Ronkainen, Marjo-Riitta Järvelin, Sylvain Sebert

Being born preterm at very low birth weight has major implications for later health and chronic disease risk factors. The mechanism linking preterm birth to later outcomes remains unknown. The findings from this study suggest an epigenetic mark of preterm birth present in adulthood, which opens up opportunities for mechanistic studies.

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SPOTLIGHT: Green space exposure and blood DNA methylation at birth and in childhood – a multi-cohort study (June 2024)

01/06/2024 - Sofia Aguilar-Lacasaña, Irene Fontes Marques et al. Environment International. LongITools authors: Irene Marques, Lucinda Calas, Ahmed Elhakeem, Barbara Heude, Vincent Jaddoe and Janine Felix - Erasmus MC, National Institute of Medical Research, University of Bristol

Green space exposure has been associated with improved mental, physical and general health. However, the underlying biological mechanisms remain largely unknown. The aim of this study was to investigate the associations of green space exposure with DNA methylation in cord and childhood blood. We found that exposure to residential green space is associated with three differentially methylated regions (DMRs) in cord blood, and with one DMR in child blood.

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Brain activity during Stroop task performance at age 74 after exposure to the Dutch famine during early gestation (June 2024)

01/06/2024 - Amber Boots et al. Brain and Cognition. LongITools authors: Amber Boots, Aline Marileen Wiegersma, Tessa J Roseboom and Susanne R de Rooij - Amsterdam University Medical Centers, location AMC
Cohort(s): Dutch Famine Birth Cohort

The Stroop Color-Word Interference test is a well-established cognitive task that measures an individual’s ability to suppress automatic responses and selectively focus attention on relevant stimuli. Performance on the task usually gets worse with increasing age. In this study, we measured brain activity during this task in people who had and had not been exposed to under nutrition during pregnancy, but we did not find clear differences between the two groups.

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The role of lifestyle factors in the association between early-life stress and adolescent psycho-physical health: Moderation analysis in two European birth cohorts (May 2024)

01/05/2024 - Serena Defina et al. Preventive Medicine. LongITools authors: Janine Felix - Erasmus MC

Early-life stress is associated with a higher risk of developing comorbidity of mental and physical health problems, including depression and obesity. Physical activity, sleep and diet did not attenuate this association, but we found some evidence that more frequent physical activity may be associated with a reduction in psycho-physical comorbidity.

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Prenatal Exposure to the 1944-45 Dutch Famine and Risk for Dementia up to Age 75: An Analysis of Primary Care Data (May 2024)

29/07/2024 - Aline Marileen Wiegersma et al. Current Alzheimer Research. LongITools authors: Amber Boots, Tessa Roseboom and Susanne de Rooij

In this population-based study using primary care data we investigated whether dementia incidence up to age 75 was higher among individuals who had been exposed to famine prenatally, which was not the case.

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Social inequalities in pregnancy metabolic profile: findings from the multi-ethnic Born in Bradford cohort study (April 2024)

30/04/2024 - Ahmed Elhakeem et al. BMC Pregnancy and Childbirth. LongITools authors: Ana Goncalves Soares - University of Bristol

Lower socioeconomic position (SEP) associates with adverse pregnancy and perinatal outcomes and with less favourable metabolic profile in nonpregnant adults. Socioeconomic differences in pregnancy metabolic profile are unknown. In this study, researchers found widespread socioeconomic differences found in metabolic traits in pregnant White European and South Asian women characterised by more adverse levels of metabolic traits in lower socioeconomic subgroups, with statistical evidence of stronger associations for some of the metabolic traits in White European than South Asian women.

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Gestational epigenetic age and ADHD symptoms in childhood: a prospective, multi-cohort study (April 2024)

02/04/2024 - Kristina Salontaji et al. Molecular Psychiatry. LongIToos authors: Janine Felix - Erasmus MC

There is an association of lower gestational age, either measured clinically or using epigenetic gestational age, with ADHD symptoms in childhood. However, epigenetic age acceleration does not provide unique information about ADHD risk independent of clinical gestational age at birth.

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Genome-wide characterization of circulating metabolic biomarkers (March 2024)

06/03/2024 - Minna K. Karjalainen et al. Nature. LongITools authors: Marjo-Riitta Järvelin, Nicholas J. Timpson - Imperial College London, University of Bristol, University of Oulu

This study identified more than 400 independent loci for NMR-measured metabolic traits, highlighting the importance of sample and participant characteristics that can have significant effects on genetic associations. Researchers demonstrated the translational utility of comprehensively phenotyped molecular data, observed substantial genetic pleiotropy for multiple metabolic pathways and illustrates the importance of careful instrument selection in Mendelian randomization analysis. The analysis reveals a putative causal relationship between acetone and hypertension. The publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases.

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Developmental origins of psycho-cardiometabolic multimorbidity in adolescence and their underlying pathways through methylation markers: a two-cohort study (February 2024)

17/02/2024 - Priyanka Choudhary et al. European Child & Adolescent Psychiatry. LongITools authors: Justiina Ronkainen, Marjo-Riitta Jarvelin, Sylvain Sebert - University of Oulu, Imperial College London

The present study exemplifies in two different cohorts similar composite structure of in utero maternal measures and psycho-cardiometabolic traits in adolescence, providing clarity on measures with cumulative risk. The findings from cross-cohort analysis elucidate the differences in health between them and enhance the understanding of plausible common shared pathways from early life to psycho-cardiometabolic health through underlying epigenetic markers.

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Blood DNA methylation profiling identifies cathepsin Z dysregulation in pulmonary arterial hypertension (January 2024)

01/01/2024 - Anna Ulrich et al. Nature Communications. LongITools authors: Zhanna Balkhiyarova, Marjo-Riitta Jarvelin, Inga Prokopenko - Imperial College London, University of Surrey

In this study, researchers demonstrated that pulmonary artery hypertension (PAH) is associated with altered blood DNA methylation profiles, exemplified by the protease cathepsin CTSZ, which modifies pulmonary endothelial function. Cathepsins are druggable and dysregulation in circulating cathepsin Z presents a priority pathway for therapeutic investigation in PAH.

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Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes (January 2024)

29/01/2024 - Maria Carolina Borges et al. BMC Medicine. LongITools authors: Janine F. Felix, Ana Gonçalves Soares, Barbara Bodinier, Marc Chadeau-Hyam, Marjo-Riitta Jarvelin, Vincent W. V. Jaddoe, Sylvain Sebert - Erasmus MC, University of Bristol, Imperial College London, University of Oulu

The study found higher mothers’ BMI has an impact in 14 out of 20 pregnancy complications studied, including the risk of high blood pressure in pregnancy, pre-eclampsia, pregnancy diabetes, and complications of delivery, such as needing a caesarean section or induction of labour, having heavier babies and neonatal intensive care unit admission. For example, for each one kg/m2 increase in maternal BMI, there was a 10% increased risk of pre-eclampsia.

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SPOTLIGHT: Prenatal urban environment and blood pressure trajectories from childhood to early adulthood (January 2024)

10/01/2024 - Ana Gonçalves Soares et al. JACC: Advances. LongITools authors: Ana Gonçalves Soares, Emie Seyve, Soile Puhakka, Aino-Maija Eloranta, Santtu Mikkonen, Wen Lun Yuan, Johanna Lepeule, Vincent Jaddoe, Timo Lakka, Sylvain Sebert, Barbara Heude, Janine Felix, Ahmed Elhakeem, Nic Timpson - University of Bristol, University of Oulu, Erasmus MC, National Institute of Medical Research, University of Eastern Finland
Cohort(s): ALSPAC, Generation R, PANIC, EDEN and NFBC 1986

We assessed the association of various characteristics of the urban environment in pregnancy with blood pressure trajectories from childhood to early adulthood. We explored measures of noise, air pollution, built environment, natural spaces, traffic, meteorology and unhealthy food environment, and found that prenatal outdoor temperature and humidity could influence blood pressure trajectory, especially in childhood.

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Defining type 2 diabetes polygenic risk scores through colocalization and network-based clustering of metabolic trait genetic associations (January 2024)

10/01/2024 - Ghatan S. et al. Genome Medicine. LongITools authors: Janine F. Felix, Maryam Kavousi, Vincent W. Jaddoe - Erasmus MC

We used genetic variants associated with type 2 diabetes (T2D) to better understand the various forms of T2D and the biological mechanisms underlying them. The research can also help in dividing patients with T2D into risk groups.

SPOTLIGHT: Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes (January 2024)

16/01/2024 - J.P. Bradfield et al. Genome Biology. LongITools authors: Zhanna Balkiyarova, Anni Heiskala, Janine Felix, Vincent Jaddoe, Marjo-Riitta Järvelin, Sylvain Sebert, Nicholas Timpson and Inga Prokopenko - University of Surrey, Erasmus MC, University of Oulu, Imperial College London, University of Bristol

The researchers report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single “optimal” pubertal growth pattern.

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A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation (January 2024)

09/01/2024 - Shaobo Li et al. Communications Biology. LongITools, Irene Marques, Justiina Ronkainen, Sylvain Sebert, Vincent Jaddoe and Janine Felix - Erasmus MC, University of Oulu

Birth order, the ordinal position of a child within their family, is associated with widespread newborn differential DNA methylation. These differences provide a catalogue of associations which can be assessed as causal mediators in the aetiology of health conditions related to birth order. Overall, we found birth order has widespread associations with DNA methylation in cord blood. Associations of differential DNA methylation at the identified sites with birth order-related health outcomes could help determine a potential mediating role of DNA methylation.

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SPOTLIGHT: Associations of low levels of air pollution with cardiometabolic outcomes and the role of diet quality in individuals with obesity (December 2023)

06/12/2023 - Darren Healy et al. Environmental Research. LongITools authors: Darren Healy, Anna Kårlund, Santtu Mikkonen, Marjukka Kolehmainen - University of Eastern Finland

Air pollutants, especially particulate matter, were found to be associated with cardiometabolic outcomes, even at average concentrations below the recently updated World Health Organisation’s air quality guidelines. Despite the very-low concentrations, diet quality appeared to modify several associations of air pollutants with cardiometabolic outcomes.

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SPOTLIGHT: Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence (December 2023)

05/12/2023 - Priyanka Choudhary et al. Molecular Psychiatry. LongITools authors: Vincent Jaddoe, Marjo-Riitta Järvelin, Justiina Ronkainen, Janine Felix and Sylvain Sebert - University of Oulu, Erasmus MC, Imperial College London

This Pregnancy And Childhood Epigenetics (PACE) Consortium study, including LongITools researchers, identified that maternal education attainment levels at the time of pregnancy were associated with offspring epigenetic markers at birth, in childhood and adolescence. The gene expression of the identified epigenetic markers is found to be involved in important biological processes. This is an important finding highlighting that socio-economic factors such as maternal education leave a “biological residue” which in turn may influence development, health, and wellbeing of the offspring. These findings form a bridge between socio-economic factors and biology. Furthermore, our results were substantially enriched for findings from previous studies on other prenatal exposures, such as maternal folate concentrations, vitamin B12 concentrations, smoking, and pre-pregnancy BMI, suggesting that maternal educational attainment level encapsulates a complex system of prenatal lifestyle-related exposures. Therefore, investing in education access, especially in low-resource settings, holds potential to reduce health inequalities and improve the well-being across generations.

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Ultra‑processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis (November 2023)

29/07/2024 - Fernanda Morales-Berstein et al. European Journal of Nutrition. LongITools authors: Ana Goncalves-Soares, - University of Bristol

Researchers investigated the role of adiposity in the association between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in more than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We found that higher consumption of UPF was associated with higher risk of both HNC and OAC. Adiposity mediated part (5-15%) of the association between UPF consumption and risk of HNC and OAC.

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Associations of Arterial Thickness, Stiffness, and Blood Pressure With Brain Morphology in Early Adolescence: A Prospective Population-Based Study (November 2023)

09/11/2023 - Serena Defina et al. Hypertension. LongITools authors: Janine Felix and Vincent Jaddoe. - Erasmus MC
Cohort(s): Generation R

Arterial wall thickness and stiffness, and high blood pressure have been repeatedly associated with poorer brain health. However, previous studies largely focused on mid- or late-life stages. It is unknown whether any arterial health–related brain changes may be observable already in adolescence. In this study, researchers found blood pressure, but not arterial wall thickness and stiffness, is associated with brain structure in early adolescence.

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Maternal caffeine consumption during pregnancy and offspring cord blood DNA methylation: an epigenome-wide association study meta-analysis (November 2023)

29/11/2023 - Laura Schellhas et al. Epigenomics. LongITools authors: Janine Felix and Vincent Jaddoe - Erasmus MC

To explore the link between caffeine intake during pregnancy and DNA methylation (DNAm) at birth, researchers analysed data from 3725 mother–child pairs living in different European countries. We looked at the effects of coffee, tea and cola intake during pregnancy on children’s DNAm at birth. We found one change in DNAm to be connected to total caffeine and another to cola consumption during pregnancy. These few connections do not provide convincing evidence that caffeine intake during pregnancy impacts children’s DNAm at birth. However, because mothers in our study consumed little caffeine, it is possible that results would be different in studies with participants consuming high amounts of caffeine during pregnancy.

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A novel approach to risk exposure and epigenetics – the use of multidimensional context to gain insights into the early origins of cardiometabolic and neurocognitive health (November 2023)

27/11/2023 - Jane W. Y. Ng, Janine F. Felix and David M. Olson. BMC Medicine. LongITools authors: Janine Felix. - Erasmus MC

This paper describes patterns of variability in DNA methylation (DNAm) using a context-based approach. Compared to previous literature, DNAm patterns exhibited novel spatial distribution across the genome that intersects with chromatin functional and tissue-specific signatures.

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SPOTLIGHT: A bidirectional Mendelian randomisation study to evaluate the relationship between body constitution and hearing loss (October 2023)

31/10/2023 - Yiyan He et al. Scientific Reports. LongITools authors: Yiyan He, Anna Pulakka, and Sylvain Sebert - University of Oulu

This paper evaluated the causal relationships between hearing loss and obesity-related traits using a bidirectional Mendelian randomisation study. The evidence was found that age-related hearing impairment was negatively associated with BMI and body fat percentage in the European ancestry adult population.

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Associations of maternal education, proximity to greenspace during pregnancy and gestational diabetes with BMI from early childhood to early adulthood: A proof-of-concept federated analysis in eighteen birth cohorts (October 2023)

19/10/2023 - Tim Cadman et al. American Journal of Epidemiology. LongITools authors: Ahmed Elhakeem, Barbara Heude, Vincent Jaddoe and Sylvain Sebert - University of Bristol, National Institute of Medical Research, Erasmus MC, University of Oulu

In this individual participant data meta-analysis of 18 cohort studies and 206,180 children, researchers explored the feasibility and utility of multicohort federated analysis by examining associations between key pregnancy exposures and BMI across childhood. They found consistent evidence that lower maternal education was associated with increased childhood BMI. Replicating and extending previous research,they found this association to emerge from ages 4 to 7 years and increase in magnitude with age. Consistent with previous studies showing a positive association between exposure to green vegetation and birthweight, this study showed that higher NDVI was associated with slightly higher BMI in the first year of life, although associations at older ages were close to null. Researchers also found evidence that gestational diabetes was associated with higher child BMI at ages 8–13 but not at younger ages.

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Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth (October 2023)

05/10/2023 - Robin N. Beaumont et al. Nature Genetics. LongITools authors: Justiina Ronkainen, Sylvain Sebert, Timo Lakka, Janine Felix, Vincent Jaddoe, Marjo-Riitta Järvelin - Erasmus MC, University of Oulu, Imperial College London, University of Eastern Finland

A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Understanding the genetic background of placental growth can help in unravelling the mechanisms underlying a healthy placenta. Researchers examined associations of genetic variants with placental weight using genome-wide association studies with genetic data from over 65,000 fetuses, over 61,000 mothers and over 52,000 fathers. They found 40 genetic variants associated with placental weight, used as a proxy for placental growth. Further analyses indicated that higher placental weight is causally associated with pre-eclampsia risk and shorter pregnancy duration.

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Epigenome-Wide Meta-analysis Reveals Associations Between Dietary Glycemic Index and Glycemic Load and DNA Methylation in Children and Adolescents of Different Body Sizes (September 2023)

26/09/2023 - Raffael Ott et al. Diabetes Care. LongITools authors: Sylvain Sebert, Marjo-Riitta Jarvelin - University of Oulu, Imperial College London

Researchers identified 537 epigenetic associations with dietary glycaemic index (GI) and glycaemic load (GL), mainly in children and adolescents with overweight or obesity. High-GI and/or -GL diets may influence epigenetic gene regulation and thereby promote metabolic derangements in young people.

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SPOTLIGHT: Random glucose GWAS in 493,036 individuals provides insights into diabetes pathophysiology, complications and treatment stratification (September 2023)

07/09/2023 - Lagou, V. et al. Nature Genetics. LongITools authors: Zhanna Balkhiyarova, Inga Prokopenko - University of Surrey

This is the largest-ever study into the genetic basis of random ‘round-the-clock’ blood sugar levels. It revealed that high blood sugar levels in type 2 diabetes can play a causal role in lung disorders. Healthcare professionals should be alert to lung disorders as a potential complication of type 2 diabetes, alongside kidney disease, heart attack and stroke

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Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude (September 2023)

11/09/2023 - Latha Kadalayil et al. Clinical Epigenetics. LongITools authors: Janine Felix, Vincent Jaddoe and Johanna Lepeule - Erasmus MC, National Institute of Medical Research

In this large epigenome-wide meta-analysis study, we provide evidence for (i) associations between DNA Methylation (DNAm) and season of birth that are unique for the seasons of the year (temporal effect) and (ii) latitude-dependent variations in the seasonal associations (spatial effect). DNAm could play a role in the molecular mechanisms underlying the effect of birth season on adult health outcomes.

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Cardiometabolic risk estimation using exposome data and machine learning (September 2023)

12/09/2023 - Angélica Atehortúa et al. International Journal of Medical Informatics. LongITools authors: Angélica Atehortúa, Marina Camacho, Maria Bulgheroni, Valentina Simonetti, Marc Chadeau-Hyam, Janine F. Felix, Sylvain Sebert and Karim Lekadir. - University of Barcelona, Ab.Acus, Erasmus MC, University of Oulu, Imperial College London
Cohort(s): UK Biobank

The human exposome encompasses all exposures that individuals encounter throughout their lifetime. It is now widely acknowledged that health outcomes are influenced not only by genetic factors but also by the interactions between these factors and various exposures. Personalised early risk assessment based on exposome attributes might be a promising tool for identifying individuals at high risk of cardiovascular disease and type 2 diabetes. Our study resulted in an exposome-based machine learning model that predicts the risk of disease by using a large dataset and outperforms a well-established tool, the Framingham risk, and performs comparably to a more integrative model requiring clinical information.

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Keeping It in the Family: Consanguinity Reveals P4HTM as a Novel Syndromic Obesity Gene (August 2023)

21/08/2023 - Janine F. Felix and Struan Grant. Diabetes. LongITools authors: Janine Felix - Erasmus MC

This is a commentary to a published paper by Saeed et al (Saeed S, Ning L, Badreddine A, et al. Biallelic mutations in P4HTM cause syndromic obesity. Diabetes 2023;72:1228–1234), in which we describe the importance of identifying rare genetic variants for severe obesity for customised treatment strategies.

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The impact of adversities across the lifespan on psychological symptom profiles in late adulthood: a latent profile analysis (July 2023)

21/07/2023 - Charlotte E Hilberdink et al. Journal of Developmental Origins of Health and Disease. LongITools authors: Tessa Roseboom and Susanne de Rooij - Amsterdam University Medical Centers, location AMC
Cohort(s): Dutch Famine Birth Cohort

People commonly face adverse circumstances throughout life, which increases the risk for psychiatric disorders, such as anxiety, depression, psychosis, and post-traumatic stress disorder (PTSD). This study showed that adversity during different periods across the lifespan has adverse consequences for psychological health lasting into late adulthood. It also showed that the impact of adversity depends on when during the lifetime it takes place and whether you are male or female.

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Bi-directional Mendelian randomization and multi-phenotype GWAS show causality and shared pathophysiology between depression and type 2 diabetes (July 2023)

26/07/2023 - Jared G. Maina et al. Diabetes Care. LongITools authors: Zhanna Balkhiyarova, Anna Ulrich, and Inga Prokopenko - University of Surrey

Our study reveals the complexity in the depression-diabetes relationship and our results have important implications for a more efficient prevention of type 2 diabetes from early adulthood when depressive symptoms usually occur.

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Effects of prenatal exposure to the 1944-45 Dutch famine and glucocorticoid receptor polymorphisms on later life PTSD susceptibility (June 2023)

19/06/2023 - Kayleigh D Gultig et al. European Journal of Psychotraumatology. LongITools authors: Susanne R. de Rooij, Tessa J. Roseboom - Amsterdam University Medical Centers, location AMC
Cohort(s): Dutch Famine Birth Cohort

Adversity during pregnancy is thought to increase offspring's risk for post-traumatic stress disorder (PTSD) following later life trauma, but exact neurobiological mechanisms underlying this process remain unknown. We found that the effects of prenatal famine exposure on PTSD symptom severity were influenced by genetic variation in the glucocorticoid receptor (GR), which signals effects of the stress hormone cortisol.

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Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes (May 2023)

01/05/2023 - Liam McAllan et al. Nature Communications. LongITools authors: Vasiliki Lagou and Inga Prokopenko - University of Surrey

DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Researchers combined epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. The results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions.

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Mediators of the association between childhood body mass index and educational attainment: Analysis of a UK prospective cohort study (May 2023)

04/05/2023 - Bowman K. et al. Pediatric Obesity. LongITools authors: Ana Gonçalves Soares - University of Bristol
Cohort(s): ALSPAC

Higher BMI in childhood was associated with lower educational attainment in adolescence. The detrimental effect of higher BMI on educational attainment appears to be partly explained by externalizing behaviours, particularly in females.

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Abdominal obesity is a more important causal risk factor for pancreatic cancer than overall obesity (May 2023)

10/05/2023 - Jared G. Maina et al. European Journal of Human Genetics. LongITools authors: Zhanna Balkhiyarova, Anna Ulrich, and Inga Prokopenko - University of Surrey

Researchers assessed the relationship between pancreatic cancer and two distinct measures of obesity, namely total adiposity, using BMI, versus abdominal, using BMI adjusted waist-to-hip ratio (WHRadjBMI) using polygenic scores (PGS) and Mendelian randomization (MR). The study shows that abdominal adiposity measured using WHRadjBMI, is a more important causal risk factor for pancreatic cancer compared to total adiposity, with T2D being a potential driver of this relationship.

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Investigating effect modification between childhood maltreatment and genetic risk for cardiovascular disease in the UK Biobank (May 2023)

04/05/2023 - Helena Urquijo et al. PLOS One. LongITools authors: Ana Goncalves Soares - University of Bristol
Cohort(s): UK Biobank

The effects of genetic susceptibility to a higher body mass index (BMI) may be moderately accentuated in individuals exposed to childhood maltreatment. However, gene environment interactions are likely not a major contributor to the excess burden of cardiovascular disease (CVD) experienced by childhood maltreatment victims.

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Metabolic profiles reflect weight loss maintenance and the composition of diet after very-low-energy diet (May 2023)

16/05/2023 - Mari Näätänen et al. Clinical Nutrition. LongITools authors: Anna Kårlund, Santtu Mikkonen, Anton Klåvus, Otto Savolainen, Kati Hanhineva, Marjukka Kolehmainen, Mari Näätänen - University of Eastern Finland

Food is one of the main environmental exposures. With this study we investigated weight loss induced metabolites could be differentiated from those resulted from food exposures. We investigated after-weight-loss metabolic signatures of two isocaloric 24-wk weight maintenance diets differing in satiety value due to dietary fibre, protein and fat contents and identified metabolite features that associated with successful weight loss maintenance.

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Maternal Diet Quality During Pregnancy and Offspring Hepatic Fat in Early Childhood: The Healthy Start Study (April 2023)

01/04/2023 - Cohen C.C. et al. Journal of Nutrition. LongITools authors: Janine Felix, Leanne Küpers - Erasmus MC

Poorer maternal diet quality during pregnancy is associated with greater offspring susceptibility to hepatic fat in early childhood. Our findings provide insights into potential perinatal targets for prevention of pediatric nonalcoholic fatty liver disease.

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A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation (April 2023)

24/04/2023 - Monasso G.S. et al. Epigenetics. LongITools authors: Vincent Jaddoe and Janine Felix - Erasmus MC

We meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy (2,420 mother-child pairs from four cohorts) or in cord blood (1,029 mother-child pairs from two cohorts), with cord blood DNA methylation. Overall, we showed that maternal and newborn vitamin B12 concentrations are associated with DNA methylation at multiple CpGs in offspring blood. Whether this differential DNA methylation underlies associations of vitamin B12 concentrations with child health outcomes, such as birth weight, gestational age, and childhood cognition, should be further examined in future studies.

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Epigenome-wide meta-analysis of prenatal maternal stressful life events and newborn DNA methylation (March 2023)

10/03/2023 - Kotsakis Ruehlmann A. et al. Molecular Psychiatry. LongITools authors: Janine Felix - Erasmus MC

Prenatal maternal stressful life events are associated with adverse neurodevelopmental outcomes in offspring. Biological mechanisms underlying these associations are largely unknown, but DNA methylation likely plays a role. The study showed that children whose mothers reported higher levels of stressful life events during pregnancy exhibited differential methylation at a number of sites in the genome. The findings give more insight into potential mechanisms of neurodevelopment in offspring, although associations with health outcomes need to be further studied.

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Shaping the risk for late-life neurodegenerative disease: A systematic review on prenatal risk factors for Alzheimer’s disease-related volumetric brain biomarkers (March 2023)

13/03/2023 - Amber Boots et al. Neuroscience & Biobehavioral Reviews. LongITools authors: Amber Boots, Aline Marileen Wiegersma, Tessa J Roseboom and Susanne R de Rooij - Amsterdam University Medical Centers, location AMC

The purpose of this systematic review was to summarize all currently available evidence for the association between prenatal exposures and Alzheimer’s Dementia (AD)-related volumetric brain biomarkers. The findings were based on 79 included studies of prenatal exposure to alcohol, opioids, cocaine, nutrient shortage, placental dysfunction and anaemia were related to smaller volumes of AD-related brain regions.

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Depression, cardiometabolic disease, and their co-occurrence after childhood maltreatment: an individual participant data meta-analysis including over 200,000 participants (March 2023)

10/03/2023 - Souama C. et al. BMC Medicine. LongITools authors: Janine Felix, Vincent Jaddoe and Karim Lekadir - Erasmus MC, University of Barcelona

Adults with a history of childhood maltreatment suffer more often from depression and cardiometabolic disease than their non-exposed peers. These adults are also three times more likely to have comorbid depression and cardiometabolic disease. Childhood maltreatment may therefore be a clinically relevant indicator connecting poor mental and somatic health. This meta-analysis revealed that adults with a history of childhood maltreatment suffer more often from depression and cardiometabolic disease than their non-exposed peers. These adults are also three times more likely to have comorbid depression and cardiometabolic disease. Childhood maltreatment may therefore be a clinically relevant indicator connecting poor mental and somatic health.

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Associations between dietary intake and glucose tolerance in clinical and metabolomics-based metabotypes (March 2023)

10/03/2023 - Amanda Rundblad et al. Genes & Nutrition. LongITools authors: Amanda Rundblad, Kirsten B. Holven and Stine M. Ulven - University of Oslo

Metabolites interact with the food we eat and are involved in determining disease risk. A metabotype is a group of people with similar composition of metabolites, that may have a similar food-disease interaction, and may thus benefit from precision nutritional recommendations. We created simple clinical metabotypes based on three glycemic variables and omics-based metabotypes based on 168 different NMR metabolomics variables. Further, we analysed interactions between habitual dietary intake and the different metabotypes on glucose tolerance.

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The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study (February 2023)

14/02/2023 - Ville Karhunen et al. BMJ Medicine. LongITools authors: Sylvain Sebert, Marjo-Riitta Järvelin - University of Oulu, Imperial College London

This study offers insight into inflammatory mediators of cardiometabolic risk factors, cytokine signalling cascades, and effects of circulating cytokines on different cardiometabolic outcomes.

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Maternal prenatal cholesterol levels predict offspring weight trajectories during childhood in the Norwegian Mother, Father and Child Cohort Study (February 2023)

06/02/2023 - Linn K. L. Øyri et al. BMC Medicine. LongITools authors: Sylvain Sebert, Stine M. Ulven and Kirsten B. Holven - University of Oslo, University of Oulu

We used data from the Norwegian Mother, Father and Child cohort data and found that maternal total cholesterol, HDL-cholesterol and apoA1 were strongly associated with offspring body weight during childhood.

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SPOTLIGHT: Effect of common pregnancy and perinatal complications on offspring metabolic traits across the life course: a multi-cohort study (January 2023)

18/01/2023 - Elhakeem A. et al. BMC Medicine. LongITools Authors: Ahmed Elhakeem, Justiina Ronkainen, Marjo-Riitta Jarvelin, Vincent Jaddoe, Sylvain Sebert - University of Bristol, University of Oulu, Imperial College London, Erasmus MC
Cohort(s): ALSPAC, Generation R, Northern Finland Birth Cohorts

Common pregnancy and perinatal complications may influence multiple metabolic traits in the offspring and these associations might differ with offspring age. However, this study suggests little evidence of wide-spread and long-term impact of common pregnancy and perinatal complications on offspring metabolic traits.

Exposure to the Dutch Famine in Early Gestation and Cognitive Function and Decline in Older Age (January 2023)

06/01/2023 - Aline Marileen Wiegersma et al. Nutrients. LongITools authors: Amber Boots, Tessa J Roseboom and Susanne R de Rooij - Amsterdam University Medical Centers, location AMC
Cohort(s): Dutch Famine Birth Cohort

Findings from this publication showed that prenatal undernutrition does not seem to impact cognitive decline with increasing age as measured by a cognitive test battery. However, at age 74, men exposed to famine in early gestation more often reported cognitive problems.

Associations of green and blue space exposure in pregnancy with epigenetic gestational age acceleration (January 2023)

11/01/2023 - Marques I. et al. Epigenetics. LongITools authors: Irene Marques, Susana Santos, Vincent Jaddoe and Janine Felix - Erasmus MC
Cohort(s): Generation R

Natural space exposure, such as availability and proximity to vegetation and water bodies, during pregnancy has been associated with offspring health. Epigenetic gestational age acceleration, a discrepancy between clinical and DNA methylation-based gestational age, which is viewed as a measure of “biological” age, may underlie these associations. This study showed that maternal exposure to green and blue spaces during pregnancy is not associated with offspring epigenetic gestational age acceleration.

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Fetal exposure to phthalates and bisphenols and DNA methylation at birth: the Generation R Study (October 2022)

10/10/2022 - Sol C.M. et al. Clinical Epigenetics. LongITools authors: Susana Santos, Vincent Jaddoe and Janine Felix. - Erasmus MC
Cohort(s): Generation R

Phthalates and bisphenols are non-persistent endocrine disrupting chemicals that are ubiquitously present in our environment and may have long-lasting health effects following fetal exposure. We examined if changes in DNA methylation are a biological mechanism that underlies these health effects. Although we did not identify genome-wide significant results, we identified some suggestive associations of exposure to a maternal mixture of phthalates and bisphenols in the first and second trimester with DNA methylation in cord blood that need further exploration in larger study samples.

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Fetal and childhood exposure to parental tobacco smoking and arterial health at age 10 years (October 2022)

18/10/2022 - Giulietta S Monasso et al. American Journal of Hypertension. LongITools authors: Janine Felix and Vincent Jaddoe - Erasmus MC

Exposure to parental tobacco smoking in fetal life and childhood was not associated with intima-media thickness and distensibility of the carotid artery, markers of arterial health, at age 10 years.

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Longitudinal associations of DNA methylation and sleep in children: a meta-analysis (July 2022)

05/07/2022 - Sammallahti S et al. Clinical Epigenetics. LongITools authors: Janine Felix and Barbara Huede. - Erasmus MC, National Institute of Medical Research
Cohort(s): ALSPAC, EDEN, GenerationR

In a meta-analysis of epigenome-wide association study results of 11 cohorts at birth and of 8 cohorts in childhood, we found no associations of DNA methylation at birth with parent-reported sleep duration, sleep initiation problems or sleep fragmentation in childhood. An association was found of lower methylation at one site each at birth with longer actigraphy-estimated sleep duration and sleep onset latency. We did not find associations of DNA methylation in childhood with sleep in childhood. The associations found with objectively measured (through actigraphy) sleep can form a basis for future research.

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Maternal dietary glycemic index and glycemic load in pregnancy and offspring cord blood DNA methylation (June 2022)

16/06/2022 - Leanne K. Küpers et al. Diabetes Care. LongITools authors: Romy Gaillard, Vincent Jaddoe and Janine Felix - Erasmus MC

Suboptimal nutrition in pregnancy is associated with worse offspring cardiometabolic health. DNA methylation may be an underlying mechanism. Researchers examined whether maternal dietary glycemic index and load are associated with cord blood DNA methylation in 2003 mother-child pairs from three cohorts. They observed multiple associations of maternal glycemic index and load during pregnancy with cord blood DNA methylation, mostly in mothers with overweight/obesity; some of these CpGs were associated with gene expression. Additional studies are required to further explore functionality, uncover causality, and study pathways to offspring health.

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Cord blood leptin level and a common variant of its receptor as determinants of the BMI trajectory: The EDEN mother-child cohort (June 2022)

23/06/2022 - Cissé A.H. et al. Pediatric Obesity. LongITools authors: Aminata H. Cissé and Barbara Heude - National Institute of Medical Research
Cohort(s): EDEN

Adiposity peak and rebound are relevant indicators of subsequent obesity and cardiometabolic risk. We analysed the role of leptin measured in cord blood, recognised as marker of neonatal fat mass, and implicated in early postnatal growth. We showed that increased leptin levels in cord blood were associated with lower BMI at adiposity peak and earlier age at adiposity rebound, characterising a high-risk BMI evolution curve for subsequent obesity. Our results suggested that cord blood leptin level could reflect an unfavourable intrauterine environment and may predict a trajectory at risk for subsequent obesity.

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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals (June 2022)

13/06/2022 - Winkler, T.W., Rasheed, H., Teumer, A. et al. Communications Biology. LongITools authors: Maryam Kavousi and Vincent Jaddoe - Erasmus MC
Cohort(s): Generation R, Rotterdam Study

Poor kidney function, as estimated by a reduced glomerular filtration rate can progress to kidney failure. Risk factors for a poor kidney function include genetic factors and diabetes, but little is known about their interaction. In this meta-analysis of genome-wide association studies we analysed the genetic background of estimated glomerular filtration rate based on serum creatinine, separately in individuals with (N=178,000) and individuals without (N=1,296,000) diabetes. We found differences between those with and those without diabetes at multiple genetic loci, showing the existence of diabetes-only and non-diabetes-only effects.

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Maternal plasma fatty acid patterns in mid-pregnancy and offspring epigenetic gestational age at birth (May 2022)

17/05/2022 - Giulietta S. Monasso et al. Epigenetics. LongITools authors: Janine Felix - Erasmus MC
Cohort(s): Generation R

Levels of fatty acids in maternal blood during pregnancy are associated with child health. Epigenetic gestational age acceleration, referring to a discrepancy between gestational age at birth and gestational age based on DNA methylation, may underlie these associations. The researchers found some evidence that a maternal plasma fatty acid pattern characterized by higher concentrations of n-3 polyunsaturated fatty acids may be associated with accelerated epigenetic gestational ageing. These findings depended on the method used and the accuracy of pregnancy dating and therefore need confirmation.

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Maternal iron status in early pregnancy and DNA methylation in offspring: an epigenome-wide meta-analysis (May 2022)

03/05/2022 - M. J. Taeubert et al. Clinical Epigenetics. LongITools authors: Janine Felix - Erasmus MC
Cohort(s): Generation R

Suboptimal, too low or too high, maternal iron status in pregnancy is associated with an increased risk of adverse birth and childhood health outcomes. DNA methylation has been suggested as a potential underlying mechanism. Maternal early-pregnancy serum ferritin concentrations, an indicator of iron status, were associated with lower cord blood DNA methylation levels at three CpGs and these associations partly persisted in older children. Further studies are needed to uncover the role of these CpGs in the underlying mechanisms of the associations of maternal iron status and offspring health outcomes.

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Maternal Glycemic Dysregulation During Pregnancy and Neonatal Blood DNA Methylation: Meta-analyses of Epigenome-Wide Association Studies (May 2022)

27/05/2022 - E.W. Tobi et al. Diabates Care. LongITools authors: Janine Felix, Barbara Huede, Vincent Jaddoe, Marjo-Riitta Järvelin and Sylvain Sebert. - University of Oulu, Erasmus MC, National Institute of Medical Research
Cohort(s): EDEN, Finnish Gestational Diabetes Study and Generation R

Analyses of oral glucose tolerance tests in pregnant women identified associations of an epigenetic marker (TXNIP) in the newborn of mothers with maternal hyperglycaemia, linked to a higher risk of type 2 diabetes. The study follows a decade of research aiming to understand how maternal glycaemic health and gestational diabetes could possibly transmit a risk of type 2 diabetes in the offspring through foetal programming.

The relationship of life-course patterns of adiposity with type 2 diabetes, depression, and their comorbidity in the Northern Finland Birth Cohort 1966 (May 2022)

13/05/2022 - Choudry P. et al. International Journal of Obesity. LongITools authors: Justiina Ronkainen, Rozenn Nedelec, Marjo-Riitta Jarvelin and Sylvain Sebert - University of Oulu, Imperial College London

Overweight since childhood was shown to be a risk factor for type 2 diabetes and co-morbidity between type 2 diabetes and depression, influenced moderately by lifestyle factors in later life. No shared early life adiposity-related risk factors were observed between type 2 diabetes and depression when assessed independently in this Finnish setting.

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Body fat, pericardial fat, liver fat and arterial health at age 10 years (May 2022)

04/05/2022 - Giulietta S. Monasso et al. Pediatric Obesity. LongITools authors: Romy Gaillard, Vincent Jaddoe and Janine Felix - Erasmus MC
Cohort(s): Generation R

Body mass index is associated with vascular health in adults and children. Researchers examined associations of general and more specific measures of adiposity with markers of arterial health in 10-year-old children. At school age, lean and fat mass seem to be related to some measures of arterial health. Arterial development might be affected by lean mass, general and specific fat mass.

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Epigenome-wide contributions to individual differences in childhood phenotypes: a GREML approach (April 2022)

19/04/2022 - Alexander Neumann et al. Clinical Epigenetics. LongITools authors: Vincent Jaddoe and Janine Felix - Erasmus MC
Cohort(s): ALSPAC, Generation R

The overall contribution of DNA methylation across the genome (R2Methylation) towards childhood phenotypes is unknown. The researchers estimated the variance explained by epigenome-wide cord blood methylation (R2Methylation) for five childhood phenotypes: gestational age, birth weight, and body mass index (BMI), IQ and ADHD symptoms at school age. The results suggest that cord blood methylation explains a moderate degree of variance in gestational age and birth weight. In contrast, a reliable estimate for school-age BMI, IQ and ADHD symptoms could not be obtained.

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Cardiovascular health at age five: distribution, determinants and association with neurodevelopment (April 2022)

11/04/2022 - Rachel E. Climie et al. Frontiers in Pediatrics. LongITools authors: Marie-Alines Charles, Barbara Heude, Jean-Philippe Empana and Rachel Climie - National Institute of Medical Research
Cohort(s): EDEN

This study showed that only a third of French children aged 5 years had ideal cardiovascular health, identified modifiable determinants of ideal cardiovascular health, and provides support for a potential association between cardiovascular health and neurodevelopment at a young age.

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Sex-specific effects of prenatal undernutrition on resting-state functional connectivity in the human brain at age 68 (April 2022)

01/04/2022 - Boots A. et al. Neurobiology of Aging. LongITools authors: Tessa Roseboom and Susanne de Rooij. - Amsterdam University Medical Centers, location AMC
Cohort(s): Dutch Famine Birth Cohort

Findings from this publication showed that prenatal undernutrition impacts functional connectivity within and between networks in the brain in late life. Exposed men showed patterns of network desegregation fitting with brain ageing.

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Maternal Mediterranean diet in pregnancy and newborn DNA methylation: a meta-analysis in the PACE Consortium (March 2022)

02/03/2022 - Leanne K. Küpersa et al. Epigenetics. LongITools authors: Vincent Jaddoe and Janine Felix - Erasmus MC
Cohort(s): ALSPAC, Generation R

Higher adherence to the Mediterranean diet during pregnancy is related to a lower risk of preterm birth and to better offspring cardiometabolic health. DNA methylation may be an underlying biological mechanism. The researchers evaluated whether maternal adherence to the Mediterranean diet was associated with offspring cord blood DNA methylation, in 2802 mother–child pairs from five cohorts. Higher adherence to the Mediterranean diet was associated with cord blood DNA methylation at cg23757341. This cytosine–phosphate–guanine (CpG) site maps to WNT5B, associated with adipogenesis and glycaemic phenotypes.

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Prenatal exposure to the Dutch famine is associated with more self-perceived cognitive problems at 72 years of age (March 2022)

02/03/2022 - Wiegersmaet A.M. al. BMC Geriatrics. LongITools authors: Tessa Roseboom and Susanne de Rooij. - Amsterdam University Medical Centers, location AMC
Cohort(s): Dutch Famine Birth Cohort

Findings from this publication showed that prenatal undernutrition does not only have lasting effects on brain size, but also on its function, with more self-perceived cognitive problems at older age, which also require more medical attention. Also, the effects of undernutrition depend on sex and its timing during gestation.

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Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation (March 2022)

22/03/2022 - Olivia Solomon et al. Mutation Research/Reviews in Mutation Research. LongITools authors: Barbara Huede, Joanna Lepeule, Janine Felix and Vincent Jaddoe. - Erasmus MC, National Institute of Medical Research
Cohort(s): ALSPAC, Generation R

There are sex-specific differences in disease prevalence, age of onset and susceptibility in multiple health conditions such as asthma and metabolic health. Differential DNA methylation may play a role in these differences. Most of those sites had lower methylation levels in males than in females. Of these differentially methylated CpG sites, 68% (31,727) also showed differences in older children ages 5.5-10 years from 8 cohorts (n = 4268). Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes. These large-scale differences in DNA methylation between the sexes may form the basis for a better understanding of the differences in disease characteristics between males and females. The exact biological mechanisms need further study.

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Using linear and natural cubic splines, SITAR, and latent trajectory models to characterise nonlinear longitudinal growth trajectories in cohort studies (March 2022)

15/03/2022 - Elhakeem A. et al. BMC Medical Research Methodology. LongITools authors: Ahmed Elhakeem - University of Bristol
Cohort(s): ALSPAC

Linear mixed effecrs models with linear and natural cubic splines, SITAR (Super Imposition by Translation and Rotation), and latent trajectory models are useful for describing nonlinear growth trajectories, and these methods can be adapted for other complex traits. Choice of method depends on the research aims, complexity of the trajectory, and available data.

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Infant weight growth patterns, childhood BMI and arterial health at age 10 years (February 2022)

10/02/2022 - Giulietta S. Monasso et al. Obesity. LongITools authors: Romy Gaillard, Vincent Jaddoe and Janine Felix - Erasmus MC
Cohort(s): Generation R

Infant peak weight velocity and BMI at adiposity peak were associated with carotid intima-media thickness in healthy children aged 10 years, independent of current BMI. Associations of infant weight growth patterns with carotid distensibility were explained by current BMI. Compared with children with normal weight, those with underweight had lower carotid intima-media thickness, whereas those with overweight had lower carotid distensibility at 10 years. These findings are important from an etiological perspective, as they suggest that both infant and childhood weight might be important for arterial health at school age. Follow-up is needed to determine whether these associations lead to adult cardiovascular disease.

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Bifidobacterium Is Enriched in Gut Microbiome of Kashmiri Women with Polycystic Ovary Syndrome (February 2022)

18/02/2022 - Hassan S. et al. Genes. LongITools authors: Marika A. Kaakinen, Zhanna Balkhiyarova and Inga Prokopenko - University of Surrey

This study supports that there is a relationship between gut microbiome composition and PCOS with links to specific reproductive health metabolic and hormonal predictors in Indian women.

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Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes (February 2022)

26/02/2022 - Pervjakova N. et al. Human Molecular Genetics. LongITools authors: Anni Heiskala, Ville Karhunen, Marjo-Riitta Järvelin and Sylvain Sebert - University of Oulu

Through multi-ancestry meta-analysis, researchers identified five loci associated with gestational diabetes mellitus (GDM), four of which that have been previously reported to associate with type 2 diabetes (T2D). Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.

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LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases (January 2022)

06/01/2022 - Justiina Ronkainen, Sylvain Sebert et al on behalf of the LongITools Project Group - University of Oulu, Erasmus MC, Imperial College London, Beta Technology, University of Eastern Finland, Chalmers University of Technology, University Medical Center Groningen, National Institute of Medical Research, University College London, Utrecht University, University of Surrey, Amsterdam University Medical Centers, location AMC, University of Oslo, University of Bristol, University of Barcelona, Ab.Acus, Cynexo, Tor Vergata University of Rome

This consortium profile paper introduces (1) LongITools’ scientific concepts that are primarily based on longitudinal modeling; (2) the metadata for the project; (3) the expected impact of the project; and finally (4) the strengths and challenges of this endeavor.

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Abuse in Childhood and Cardiometabolic Health in Early Adulthood: Evidence From the Avon Longitudinal Study of Parents and Children (December 2021)

12/12/2021 - Goncalves Soares A., Zimmerman A. et al.
Cohort(s): ALSPAC

We assessed associations between childhood physical, sexual, and psychological abuse and cardiometabolic outcomes at 18 and 25 years using data from 3,223 ALSPAC participants. We found that childhood abuse is associated with negative cardiometabolic outcomes, particularly higher body mass index (BMI) and insulin, even by young adulthood.

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MC3R links nutritional state to childhood growth and the timing of puberty (November 2021)

03/11/2021 - Lam, B.Y.H., Williamson, A., Finer, S. et al. Nature. LongITools authors: Ana Gonçalves Soares and Nic Timpson - University of Bristol
Cohort(s): ALSPAC

It has long been known that humans with good nutrition tend to grow taller and mature more quickly, and that signals about the body’s nutritional health are sent to the hypothalamus, but how this process is controlled has not previously been understood. We showed that the Melanocortin 3 receptor (MC3R) in the brain regulates the rate of linear growth and timing of sexual maturation, which are energy-sensitive processes.

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Epigenetic age acceleration and cardiovascular outcomes in school-age children: The Generation R Study (November 2021)

16/11/2021 - Giulietta S Monasso et al. Clinical Epigenetics. LongITools authors: Vincent Jaddoe and Janine Felix - Erasmus MC
Cohort(s): Generation R

In this population-based study of 1,115 children from the Generation R Study, we examined if epigenetic age acceleration at birth and school age was associated with blood pressure and vascular structure and function, measured as carotid intima-media thickness and distensibility, respectively, at age 10 years. We found no associations. Our findings do not support the hypothesis that altered epigenetic aging in early life is a biological mechanism underlying cardiovascular risk factors in childhood.

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Relationship between glucose homeostasis and obesity in early life—a study of Italian children and adolescents (September 2021)

30/09/2021 - Zhanna Balkhiyarova et al. Human Molecular Genetics. LongITools authors: Zhanna Balkhiyarova, Marika Kaakinen, Anna Ulrich and Inga Prokopenko - University of Surrey

We aimed to test if weighted genetic risk scores (GRSs) for T2D, fasting glucose (FG) and fasting insulin (FI) predict glycaemic traits and if there is a causal relationship between obesity and impaired glucose metabolism in children and adolescents. Our results demonstrate that the glycaemic and T2D risk genetic variants contribute to higher FG and FI levels and decreased beta cell function in children and adolescents. The causal effects of adiposity on increased insulin resistance are detectable from childhood age.

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Measurement invariance testing of the patient health questionnaire-9 (PHQ-9) across people with and without diabetes mellitus from the NHANES, EMHS and UK Biobank datasets (September 2021)

01/09/2021 - Nouwen A., Deschênes S.S. et al. Journal of Affective Disorders. LongITools authors: Zhanna Balkhiyarova and Inga Prokopenko - University of Surrey

The prevalence of depression is higher among those with diabetes than in the general population. The Patient Health Questionnaire (PHQ-9) is commonly used to assess depression in people with diabetes, but measurement invariance of the PHQ-9 across groups of people with and without diabetes has not yet been investigated.Results provide support for measurement invariance between groups of people with and without diabetes, using either a one-factor or a two-factor model. While the two-factor solution has a slightly better fit, the one-factor solution is more parsimonious. Depending on research or clinical needs, both factor structures can be used.

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Vitamin B12, folate and homocysteine concentrations during pregnancy and early signs of atherosclerosis at school-age (September 2021)

01/09/2021 - Giulietta S. Monasso et al. Clinical Nutrition. LongITools authors: Janine Felix, Romy Gaillard and Vincent Jaddoe. - Erasmus MC
Cohort(s): Generation R

We examined if vitamin B12, folate and homocysteine concentrations are associated with vascular structure and function in 3,826 school-age children. We found that having a low vitamin B12 concentrations in early pregnancy was related with a higher thickness of the vascular wall and having a low folate concentration in early pregnancy was associated with a higher vascular stiffness. Similarly, higher homocysteine concentrations in cord blood were associated with higher vascular stiffness. This means that suboptimal concentrations of vitamin B12, folate and homocysteine seem to be related to worse cardiovascular risk factors at school-age. Whether these associations are causal and what the exact mechanisms are need to be further studied.

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Functional Effects In Silico Prediction for Androgen Receptor Ligand-Binding Domain Novel I836S Mutation (July 2021)

06/07/2021 - Alexey Rayevsky et al. Life. LongITools authors: Inga Prokopenko - University of Surrey

Over 1000 mutations are described in the androgen receptor (AR) gene. Of those, about 600 were found in androgen insensitivity syndrome (AIS) patients, among which 400 mutations affect the ligand-binding domain (LBD) of the AR protein. Recently, we reported a novel missense mutation c.2507T>G I836S (ClinVarID: 974911) in a patient with complete AIS (CAIS) phenotype. In the present study, our analyses provide evidence that I836S causes disruptions of AR protein functionality and development of CAIS clinical features in patients.

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The determinants and longitudinal changes in vitamin D status in middle-age: a Northern Finland Birth Cohort 1966 study (June 2021)

17/06/2021 - Helmi Ikonen et al. European Journal of Nutrition. LongITools authors: Marjo-Riitta Järvelin and Sylvain Sebert - University of Oulu, Imperial College London

There is a paucity of studies to address the possible independent effect of vitamin D fortification programmes on the vitamin D status in the general population taking into account additional risk factors, including amongst other BMI, vitamin D intake from other dietary sources and supplementation as well as previous vitamin D status. We found a positive impact of the vitamin D food fortification on reducing the prevalence of serum 25(OH)D<30 nmol/L and 50 nmol/L, and seasonal variations in vitamin D status among middle-aged adults in Finland.

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Metabolic profiles of socio-economic position: a multi-cohort analysis (June 2021)

01/06/2021 - Oliver Robinson et al. International Journal of Epidemiology. LongITools authors: Marjo-Riitta Järvelin, Ville Karhunen - University of Oulu, Imperial College London

This work examined the associations between socioeconomic position and over 200 metabolic measures, and results show that lower socioeconomic position was associated with adverse metabolic profile. This finding implies that low socioeconomic position may contribute to health inequalities.

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Associations of hair cortisol concentrations with cardiometabolic risk factors in childhood (May 2021)

29/05/2021 - Florianne O L Vehmeijer et al. J Clin Endocrinol Metab. LongITools authors: Susana Santos, Vincent Jaddoe and Janine Felix - Erasmus MC
Cohort(s): Generation R

Stress is related to cardiovascular disease in adults. In a population-based study of 2,598 children, we measured hair cortisol levels at age 6 years as a marker of exposure to stress and examined if these were associated with cardiometabolic risk factors, such as blood pressure and lipid levels, at age 10 years. We did not find such associations after taking BMI into account. The associations of biological stress with cardiometabolic risk factors may develop at later ages.

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How does childhood maltreatment influence cardiovascular disease? A sequential causal mediation analysis (May 2021)

26/05/2021 - Ana G Soares et al. International Journal of Epidemiology. LongITools authors: Ana G Soares - University of Bristol
Cohort(s): UK Biobank

Although there is a robust association between childhood maltreatment and cardiovascular disease (CVD) risk, the mechanisms underlying this relationship are not yet fully understood. In this study we showed that anxiety/depression, smoking, body mass index (BMI) and inflammation mediated 26%-90% of the association between childhood maltreatment and CVD and the contribution of these mediators differed by type of maltreatment and sex.

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Associations of circulating folate, vitamin B12 and homocysteine concentrations in early pregnancy and cord blood with epigenetic gestational age: the Generation R Study (April 2021)

29/04/2021 - Monasso G.S. et al. Clinical Epigenetics. LongITools authors: Vincent Jaddoe and Janine Felix - Erasmus MC
Cohort(s): Generation R

Concentrations of folate, vitamin B12 and homocysteine during pregnancy are associated with childhood health outcomes. In a population-based study of 1,346 mothers and newborns, we found some evidence to support associations of maternal plasma homocysteine concentrations with positive epigenetic gestational age acceleration, suggesting faster epigenetic than clinical gestational ageing. Cord serum vitamin B12 concentrations may be associated with negative gestational age acceleration, indicating slower epigenetic than clinical gestational ageing.

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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight (March 2021)

09/03/2021 - NCD Risk Factor Collaboration (NCD-RisC). eLife. LongITools authors: Marjo-Riitta Järvelin and Sylvain Sebert - University of Oulu

Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.

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Cohort profile: the Dutch famine birth cohort (DFBC) – a prospective birth cohort study in the Netherlands (March 2021)

04/03/2021 - Bleker L.S. et al. BMJ Open. LongITools authors: Susanne de Rooij and Tessa Roseboom - Amsterdam University Medical Centers, location AMC
Cohort(s): Dutch Famine Birth Cohort

This paper describes the study protocol and results of the Dutch famine birth cohort study investigating the effects of prenatal exposure to famine on health across the life-course.

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COVID‐19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors (February 2021)

15/02/2021 - Elliott, J. et al. European Journal of Epidemiology. LongITools authors: Barbara Bodinier, Roel Vermeulen and Marc Chadeau‐Hyam - Imperial College London, Utrecht University
Cohort(s): UK Biobank

Several factors have been identified as driving the risk of COVID-19 mortality using routine/hospital based studies. Using general population studies we investigate the role of demographic, social, lifestyle, biological, medical and environmental data from UK Biobank in relation to COVID-19 and non-COVID-19 deaths.

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Risk of Recurrent Pregnancy Loss in the Ukrainian Population Using a Combined Effect of Genetic Variants: A Case-Control Study (January 2021)

05/01/2021 - Eleni M. Loizidou et al. Genes. LongITools authors: Marika Kaakinen and Inga Prokopenko - University of Surrey

By combining 12 genetic variants from loci reflecting the main biological pathways involved in pregnancy maintenance, we had an improved ability to classify women with and without recurrent pregnancy loss. This highlights the potential of genetics in predicting the risk of this complex multifactorial condition in women of reproductive age.

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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability (January 2021)

05/01/2021 - Lagou V. et al. Nature Communications. LongITools authors: Inga Prokopenko, Marika Kaakinen, Anna Ulrich, Nicholas Timpson, Marjo-Riitta Jarvelin - University of Surrey, Imperial College London, University of Bristol

We report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men.

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Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes – A nested case-control study (January 2021)

01/01/2021 - T. Schillemans et al. Environment International. LongITools authors: Kati Hanhineva, Rikard Landberg and Carl Brunius. - University of Eastern Finland, Chalmers University of Technology

Perfluoroalkyl substances (PFAS) are widespread persistent environmental pollutants. PFAS may impact Type 2 Diabetes (T2D) development, but findings are inconsistent. Using untargeted metabolomics, we found two groups of metabolites (diacylglycerols and glycerophospholipids) that correlated positively with PFAS. However, these two metabolite groups showed opposite associations with T2D risk, which may help to explain the conflicting results found for PFAS and T2D.

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Epigenome-wide change and variation in DNA methylation in childhood: Trajectories from birth to late adolescence (January 2021)

01/01/2021 - Rosa H Mulder et al. Human Molecular Genetics. LongITools authors: Janine Felix, Vincent Jaddoe - Erasmus MC
Cohort(s): ALSPAC, Generation R

DNA methylation is an important biological process in childhood health and development, but a comprehensive characterisation of genome-wide DNAm trajectories across this age period is currently lacking. In this manuscript, we used data from epigenome-wide association studies in 5,019 blood samples collected at multiple time-points from birth to late adolescence from 2,348 participants of two large independent cohorts to characterize DNAm trajectories over time. We found that DNAm levels change over time in more than half of the DNAm sites and we describe these changes. Our findings support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu.ac.uk.

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Paternal body mass index and offspring DNA methylation: findings from the PACE consortium (January 2021)

29/01/2021 - Gemma C Sharp et al. International Journal of Epidemiology. LongITools authors: Vincent Jaddoe, Johanna Lepeule and Janine Felix - Erasmus MC, National Institute of Medical Research

Overweight and obesity in fathers around the time of conception is related to offspring health. Changes in DNA methylation may be an underlying biological mechanism. In a large study including data from almost 5000 newborns and almost 2000 children, we did not find evidence to support this.

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DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures (January 2021)

07/01/2021 - Monica del C. Gomez‐Alonso et al. Clinical Epigenetics. LongITools authors: Sylvain Sebert and Marjo-Riitta Järvelin. - University of Oulu, Imperial College London

The study provides evidence of an independent association between DNA methylation and the lipid compositions and lipid concentrations of different lipoprotein size subclasses. It brings granularity into well‐known associations of DNA methylation with total serum lipids further supporting the need for detailed profiling of lipid-related traits.

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Post-weight loss changes in fasting appetite and energy balance-related hormone concentrations and the effect of the macronutrient content of a weight maintenance diet: a randomised controlled trial (December 2020)

02/12/2020 - Näätänen M. et al. European Journal of Nutrition. LongITools authors: Marjukka Kolehmainen, Mari Näätänen - University of Eastern Finland

The study looked at the effects of the macronutrient composition of diets with differing satiety values on fasting appetite-related hormone concentrations after weight loss and examined whether the hormone secretion adapted to changes in body fat mass and fat-free mass (FFM) during the weight maintenance period (WM). The macronutrient composition of an isoenergetic WM diet did not affect fasting appetite-related hormone concentrations. Leptin and insulin associated with the amount of the reduced fat mass, whereas ghrelin reflected FFM during the first months of the WM.

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Maternal and infant prediction of the child BMI trajectories; studies across two generations of Northern Finland Birth Cohorts (October 2020)

11/10/2020 - Rozenn Nedelec et al. International Journal of Obesity. LongITools authors: Rozenn Nedelec, Marjo-Riitta Järvelin and Sylvain Sebert - University of Oulu
Cohort(s): Northern Finland Birth Cohorts

Detrimental maternal factors were consistently associated with a higher risk obesity trajectory in two generations of Finnish birth cohorts, with a greater amplitude of the effects observed in the younger cohort. However, a discordant association between the timing of adiposity peak in relation to adverse BMI trajectories occurred over the course of a generation, adding further evidence of the link between very early mechanisms, in the first months of life, and childhood obesity.

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Expression Quantitative Trait Locus Mapping in Pulmonary Arterial Hypertension (October 2020)

22/10/2020 - Ulrich A. et al. Genes. LongITools authors: Inga Prokopenko, Anna Ulrich - University of Surrey

We demonstrate the utility of mapping expression quantitative trait loci (eQTL), which is normally done in individuals from a healthy population, in individuals with a disease. We report novel gene – eQTL pairs overlapping GWAS loci which could possibly aid in the biological interpretation of GWAS associations.

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Machine Learning-Based DNA Methylation Score for Fetal Exposure to Maternal Smoking: Development and Validation in Samples Collected from Adolescents and Adults (September 2020)

15/09/2020 - Rauschert S. et al. Environmental Health Perspectives. LongITools authors: Anni Heiskala, Ville Karhunen, Marjo-Riitta Järvelin and Sylvain Sebert - University of Oulu
Cohort(s): Northern Finland Birth Cohorts, Raine Study

Fetal exposure to maternal smoking during pregnancy is associated with the development of noncommunicable diseases in the offspring. Maternal smoking may induce such long-term effects through persistent changes in the DNA methylome, which therefore hold the potential to be used as a biomarker of this early life exposure. We have developed a DNA methylation score for exposure to maternal smoking during pregnancy. One possible application of the current score could be for model adjustment purposes or to assess its association with distal health outcomes where part of the effect can be attributed to maternal smoking. Furthermore, it may provide a biomarker for fetal exposure to maternal smoking.

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Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility (July 2020)

14/07/2020 - James Dooley et al. Cell Reports. LongITools authors: Inga Prokopenko, Anna Ulrich - University of Surrey

Pancreatic cancer is a rare but fatal form of cancer, the fourth highest in absolute mortality. Known risk factors include obesity, diet, and type 2 diabetes; however, the low incidence rate and interconnection of these factors confound the isolation of individual effects. Here, we use epidemiological analysis of prospective human cohorts and parallel tracking of pancreatic cancer in mice to dissect the effects of obesity, diet, and diabetes on pancreatic cancer. Using epidemiological approaches in humans, we find that dietary sugars give a MAD2L1 genotype-dependent increased susceptibility to pancreatic cancer. The translation of these results to a clinical setting could aid in the identification of the at-risk population for screening and potentially harness dietary modification as a therapeutic measure.

Early exposure to social disadvantages and later life body mass index beyond genetic predisposition in three generations of Finnish birth cohorts (May 2020)

18/05/2020 - Lowry, E., Rautio, N., Wasenius, N. et al. BMC Public Health. LongITools Authors: Anni Heiskala, Leena Ala-Mursula, Jouko Miettunen, Marjo-Riitta Järvelin and Sylvain Sebert - University of Oulu
Cohort(s): Northern Finland Birth Cohorts, Helsinki Birth Cohort Study

High social disadvantage in early life appears to be associated with being with higher BMI in later life. Reducing exposure to social disadvantage during the life-course reduced the risk a and may be a potential pathway for obesity reduction.

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OTHER PUBLICATIONS

A few of our publications cannot be mapped across the life-course. They can be seen in the table below.

PublicationLink
PublicationDemetris Avraam et al. DataSHIELD: mitigating disclosure risk in a multi-site federated analysis platform. Bioinformatics Advances (2025).Link

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PublicationTim Cadman et al. MOLGENIS Armadillo: a lightweight server for federated analysis using DataSHIELD. Bioinformatics (2025).Link

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PublicationVilma Liikonen et al. Association between whole grain consumption, tryptophan metabolism, and psychological distress. British Journal of Nutrition (2024). Link

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PublicationJoshua Elliott et al. Sex inequalities in cardiovascular risk prediction. Cardiovascular Research (2024). Link

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PublicationRin Wada et al. Hair-Derived Exposome Exploration of Cardiometabolic Health: Piloting a Bayesian Multitrait Variable Selection Approach. Environmental Science & Technology (2024).Link

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PublicationKhezia Asamoah et al. Proteomic signatures of eosinophilic and neutrophilic asthma from serum and sputum. eBioMedicine (2024).Link

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PublicationVincent Pascat et al. comorbidPGS: An R Package Assessing Shared Predisposition between Phenotypes Using Polygenic Scores. Human Heredity (2024).Link

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PublicationBarbara Bodinier et al. Automated calibration for stability selection in penalised regression and graphical models. Journal of the Royal Statistical Society Series C: Applied Statistics (2023). Link

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PublicationRafaella E. Sigala et al. Machine Learning to Advance Human Genome-Wide Association Studies. Genes (2023).Link

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PublicationBarbara Bodinier et al. Automated calibration of consensus weighted distance-based clustering approaches using sharp. Bioinformatics (2023).Link

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PublicationAmanda Rundblad et al. Omega-3 fatty acids and individual variability in plasma triglyceride response: A mini-review. Redox Biology (2023).Link

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PublicationAnna Cascarano et al. Machine and deep learning for longitudinal biomedical data: a review of methods and applications. Artificial Intelligence Review (2023).Link

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PublicationClayton G., Gonçalves Soares A. at al. A framework for assessing selection and misclassification bias in Mendelian randomization studies: An illustrative example between body mass index and COVID-19. BMJ (2023).Link

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PublicationIman Zarei et al. Tissue-wide metabolomics reveals wide impact of gut microbiota on mice metabolite composition. Scientific Reports (2023).Link

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PublicationT. Schillemans et al. Associations of PFAS-related plasma metabolites with cholesterol and triglyceride concentrations. Environmental Research (2023).Link

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PublicationMorris Swertz et al. Towards an Interoperable Ecosystem of Research Cohort and Real-world Data Catalogues Enabling Multi-center Studies. Yearbook of Medical (2022). InformaticsLink

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PublicationFarizah Babu A. et al. Identification and distribution of sterols, bile acids, and acylcarnitines by LC-MS/MS in humans, mice, and pigs – A qualitative analysis. Metabolites (2022).Link

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PublicationTanja Nordström et al. Cohort Profile: 46 years of follow-up of the Northern Finland Birth Cohort 1966. International Journal of Epidemiology (2021).Link

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PublicationForzano F. et al on behalf of the Executive Committee of the European Society of Human Genetics and the Public and Professional Policy Committee of the European Society of Human Genetics. The use of polygenic risk scores in pre-implantation genetic testing: an unproven, unethical practice. European Journal of Human Genetics (2021).Link

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PublicationZhang P. et al. Defining the scope of exposome studies and research needs from a multidisciplinary perspective. Environmental Science & Technology Letters (2021).Link

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PublicationKårlund A. et al. Harnessing Microbes for Sustainable Development: Food Fermentation as a Tool for Improving the Nutritional Quality of Alternative Protein Sources. Nutrients (2020). Link

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