Abstract
Pregnancy is a valuable model to study the association between DNA methylation and several cardiometabolic traits, due to its direct potential to influence mother's and child's health. Epigenetics in Pregnancy (EPIPREG) is a population-based sample with the aim to study associations between DNA-methylation in pregnancy and cardiometabolic traits in South Asian and European pregnant women and their offspring. This cohort profile paper aims to present our sample with genetic and epigenetic data and invite researchers with similar cohorts to collaborative projects, such as replication of ours or their results and meta-analysis. In EPIPREG we have quantified epigenome-wide DNA methylation in maternal peripheral blood leukocytes in gestational week 28±1 in Europeans (n = 312) and South Asians (n = 168) that participated in the population-based cohort STORK Groruddalen, in Norway. DNA methylation was measured with Infinium MethylationEPIC BeadChip (850k sites), with technical validation of four CpG sites using bisulphite pyrosequencing in a subset (n = 30). The sample is well characterized with few missing data on e.g. genotype, universal screening for gestational diabetes, objectively measured physical activity, bioelectrical impedance, anthropometrics, biochemical measurements, and a biobank with maternal serum and plasma, urine, placenta tissue. In the offspring, we have repeated ultrasounds during pregnancy, cord blood, and anthropometrics up to 4 years of age. We have quantified DNA methylation in peripheral blood leukocytes in nearly all eligible women from the STORK Groruddalen study, to minimize the risk of selection bias. Genetic principal components distinctly separated Europeans and South Asian women, which fully corresponded with the self-reported ethnicity. Technical validation of 4 CpG sites from the methylation bead chip showed good agreement with bisulfite pyrosequencing. We plan to study associations between DNA methylation and cardiometabolic traits and outcomes.
Highlights
Studies of epigenetic marks have in recent years gained increased interest in the context of human diseases [1]
Several studies have indicated that DNA methylation is associated with cardiovascular risk factors such as body mass index (BMI) [4,5,6,7], gestational diabetes (GDM) [8], type 2 diabetes (T2D) [9,10,11,12,13], lipid levels [14,15], hypertension [16,17], smoking [18,19,20,21,22] and alcohol intake [23,24,25], suggesting that cardiometabolic diseases have an epigenetic component
For Europeans, we were able to quantify DNA methylation in 99% of the eligible samples, 87.2% of the total number of Europeans participating in STORK Groruddalen (STORK G) at week 28±2
Summary
Studies of epigenetic marks have in recent years gained increased interest in the context of human diseases [1]. Pregnant women provide a unique opportunity to study the association between blood DNA methylation and several phenotypes related to glucose homeostasis and cardiovascular traits This is because pregnancy has been proposed as a stress test for metabolism in several organs [26], including the pancreatic beta-cells, since insulin resistance increase naturally in all pregnancies [27]. The aim of EPIPREG is to discover novel associations between DNA-methylation in pregnancy and cardiometabolic related traits in South Asian and European pregnant women and their offspring, which may have potential for prevention and treatment This cohort profile paper aims to present our sample with genetic and epigenetic data and invite researchers with similar cohorts to collaborative projects, such as replication of ours or their results and meta-analysis. The overall participation rate in STORK G was 74%, 81.5% for Europeans and 73% for South Asians [30]
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