Life-course publications map

Publications from the LongITools project will be 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.

Publications Map © Beta Technology Ltd 2020

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

08/04/2021 - 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.

Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

14/04/2021 - 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.

Expression Quantitative Trait Locus Mapping in Pulmonary Arterial Hypertension

15/04/2021 - 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.

Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility

15/04/2021 - 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.

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

14/04/2021 - 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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