![]() ![]() We hypothesize that high body mass index and excess weight gain in pregnancy is associated with DNA methylation of CpG sites. Although this interplay could lead to differences by ancestry, combining populations of different ancestries with genetic and environmental differences (such as different lifestyle habits) may help in the discovery of CpG sites with robust DNA methylation associated with lifestyle factors across ancestry and reduce the risk of false positives. The interplay between genetics and environmental factors may explain why some develop disease and not others. To the best of our knowledge, there are currently no EWAS in maternal peripheral blood leukocytes of BMI in pregnancy or GWG.ĭifferences in allele frequencies and linkage disequilibrium across ancestry may influence the risk of developing different diseases. A few epigenome wide association studies (EWAS) of DNA methylation in offspring tissues and placenta in association with maternal body weight have been conducted. Epidemiological studies of non-pregnant populations have identified several CpG sites across the genome with differential DNA methylation associated with BMI. There is an increasing interest in studies of how environmental factors influence epigenetic signatures such as DNA methylation and thereby modify gene expression. However, genetic variation explains only parts of the risk for obesity-related metabolic complications, wherein epigenetics are thought to influence gene expression and thereby downstream disease outcomes. Several genetic variants associated with body mass index (BMI) have also been associated with metabolic complications of obesity, such as type 2 diabetes mellitus. Overweight, obesity and excessive GWG also increases the risk of developing type 2 diabetes mellitus and cardiovascular disease later in life for both the mother and her offspring. Women who have overweight or obesity in pregnancy, or have excessive gestational weight gain (GWG), are at increased risk of pregnancy-related complications such as pre-eclampsia, gestational diabetes mellitus (GDM), and of having offspring that are large for gestational age. Not applicable Similar content being viewed by others The identified CpG sites were associated with cardiometabolic traits. Several genetic variants were associated with DNA methylation at cg02786379 and cg16733643 suggesting a genetic component influencing differential methylation. Three of the sites were replicated in an independent cohort. We identified five CpG sites associated with BMI at gestational week 28, and one with GWG. DNA methylation at the three replicated CpG sites were associated with levels of blood pressure, lipids and glucose in EPIPREG ( p from 1.2 × 10 −8 to 0.04). Two sites are located in genes previously associated with blood pressure and BMI. Of these, we were able to replicate three in MoBa-START cg02786370, cg19758958 and cg10472537. We identified one CpG site significantly associated with GWG ( p 5.8 × 10−8) and five CpG sites associated with BMI at gestational week 28 ( p from 4.0 × 10–8 to 2.1 × 10–10). Replication was performed in the Norwegian Mother, Father, and Child Cohort Study, the Study of Assisted Reproductive Technologies (MoBa-START) ( n = 877, mainly European/Norwegian). In women with European ( n = 303) and South Asian ( n = 164) ancestry, we performed an epigenome-wide association study of BMI in gestational week 28 and GWG between gestational weeks 15 and 28 using a meta-analysis approach. In the Epigenetics in pregnancy (EPIPREG) sample we quantified maternal DNA methylation in peripheral blood leukocytes in gestational week 28 with Illumina’s MethylationEPIC BeadChip. Furthermore, we aimed to investigate how the identified sites were associated with methylation quantitative trait loci, gene ontology, and cardiometabolic parameters. ![]() ![]() We aimed to discover CpG sites with differential DNA methylation in peripheral blood leukocytes associated with body mass index (BMI) in pregnancy and gestational weight gain (GWG) in women of European and South Asian ancestry. ![]()
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