Dataset Information

Variants in BMI-Associated Genes and Adrenergic Genes are not Associated with Gestational Weight Trajectory.

ABSTRACT: OBJECTIVE:The aim of this study is to define the association between a genetic risk score (GRS) that combined the effect of multiple BMI-associated variants and gestational weight trajectory. Because pregnancy is a state of sympathetic activation, the association between gestational weight trajectory and variants in adrenergic pathways previously associated with weight was examined. METHODS:In a previously defined cohort of pregnant women with (n = 1,504) and without gestational diabetes (GDM) (n = 435), weight trajectory was calculated using all weights during pregnancy. A GRS for BMI (GRSBMI ) was calculated using 31 common variants associated with BMI, and 10 variants in the adrenergic pathways were genotyped. Clinical and genetic factors were studied using generalized linear models. RESULTS:Prepregnancy BMI was associated with the GRSBMI (P = 9.3 × 10-11 ) and parity (P = 4.54 × 10-17 ). The GRSBMI was associated with gestational weight trajectory in women with and without GDM (P = 0.041 and P < 0.0001, respectively); however, when prepregnancy BMI was included in the models, the associations disappeared (P > 0.05). Variants in adrenergic genes were not associated with gestational weight trajectory. CONCLUSIONS:A GRS for BMI was associated with prepregnancy BMI but was not independently associated with gestational weight trajectory in women with and without GDM. Selected variants in adrenergic genes were not associated with gestational weight trajectory.

SUBMITTER: Kawai VK

PROVIDER: S-EPMC6591076 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Variants in BMI-Associated Genes and Adrenergic Genes are not Associated with Gestational Weight Trajectory.

Kawai Vivian K VK Nwosu Samuel K SK Kurnik Daniel D Harrell Frank E FE Stein C Michael CM

Obesity (Silver Spring, Md.) 20190522 7

<h4>Objective</h4>The aim of this study is to define the association between a genetic risk score (GRS) that combined the effect of multiple BMI-associated variants and gestational weight trajectory. Because pregnancy is a state of sympathetic activation, the association between gestational weight trajectory and variants in adrenergic pathways previously associated with weight was examined.<h4>Methods</h4>In a previously defined cohort of pregnant women with (n = 1,504) and without gestational d ...[more]

PMID: 31116007

Similar Datasets

Project description:BackgroundMaternal obesity prior to or during pregnancy influences fetal growth, predisposing the offspring to increased risk for obesity across the life course. Placental epigenetic mechanisms may underlie these associations. We conducted an epigenome-wide association study to identify placental DNA methylation changes associated with maternal prepregnancy body mass index (BMI) and rate of gestational weight gain at first (GWG1), second (GWG2), and third trimester (GWG3).MethodParticipants of the NICHD Fetal Growth Studies with genome-wide placental DNA methylation (n = 301) and gene expression (n = 75) data were included. Multivariable-adjusted regression models were used to test the associations of 1 kg/m2 increase in prepregnancy BMI or 1 kg/week increase in GWG with DNA methylation levels. Genes harboring top differentially methylated CpGs (FDR P < 0.05) were evaluated for placental gene expression. We assessed whether DNA methylation sites known to be associated with BMI in child or adult tissues, were also associated with maternal prepregnancy BMI in placenta.ResultsPrepregnancy BMI was associated with DNA methylation at cg14568196[EGFL7], cg15339142[VETZ], and cg02301019[AC092377.1] (FDR P < 0.05, P ranging from 1.4 × 10-10 to 1.7 × 10-9). GWG1 or GWG2 was associated with DNA methylation at cg17918270[MYT1L], cg20735365[DLX5], and cg17451688[SLC35F3] (FDR P < 0.05, P ranging from 6.4 × 10-10 to 1.2 × 10-8). Both prepregnancy BMI and DNA methylation at cg1456819 [EGFL7] were negatively correlated with EGFL7 expression in placenta (P < 0.05). Several CpGs previously implicated in obesity traits in children and adults were associated with prepregnancy BMI in placenta. Functional annotations revealed that EGFL7 is highly expressed in placenta and the differentially methylated CpG sites near EGFL7 and VEZT were cis-meQTL targets in blood.ConclusionsWe identified placental DNA methylation changes at novel loci associated with prepregnancy BMI and GWG. The overlap between CpGs associated with obesity traits in placenta and other tissues in children and adults suggests that epigenetic mechanisms in placenta may give insights to early origins of obesity.

Project description:BackgroundFew studies have investigated the associations of childhood growth trajectories with the prenatal metabolic risks of mothers and their interaction with children's genetic susceptibility.ObjectiveTo investigate the effects of gestational metabolic syndrome (GMS) risks and children's polygenic risk scores (PRSs), and their interaction effect on the BMI trajectory and obesity risk of offspring from birth to 6 years of age.MethodsA total of 2,603 mother-child pairs were recruited from the Ma'anshan birth cohort (Anhui Province of China) study. Data on maternal prepregnancy obesity, gestational weight gain (GWG), gestational diabetes mellitus (GDM), and hypertensive disorders of pregnancy (HDP) were used to evaluate maternal GMS risk. In addition, 1,482 cord blood samples were used to genotype 11 candidate single-nucleotide polymorphisms (SNPs) to calculate children's PRSs. The latent class growth model using the longitudinal BMI-for-age z scores (BMIz) was applied to validly capture the BMIz growth trajectory.ResultsMaternal GMS status was associated with higher BMIz scores and with an increased risk of overweight/obesity. Positive relationships were revealed between PRS and the risk of overweight/obesity among girls. Additionally, maternal GMS significantly interacted with the child's PRS on BMIz scores and the risk of overweight/obesity among girls. Hierarchical BMI trajectory graphs by different exposure groups showed consistent findings, and both boys' and girls' BMIz trajectories were divided into three groups. Among girls, the higher the GMS risk or PRS they had, the higher the probability of being in the high BMIz trajectory group.ConclusionsMaternal GMS status increased BMIz scores and the risk of obesity in both boys and girls and elevated the child's BMI trajectory from birth to 6 years of age among girls. PRSs were significantly associated with children's BMI trajectory and the risk of obesity and modified the associations between maternal GMS status and obesity biomarkers only among girls. Thus, regarding childhood obesity, steps should be taken to decrease maternal metabolic risks before and during pregnancy, and sex discrepancies should be noted to identify high-risk populations after birth to hierarchically manage them.

Dataset Information

Variants in BMI-Associated Genes and Adrenergic Genes are not Associated with Gestational Weight Trajectory.

Publications

Variants in BMI-Associated Genes and Adrenergic Genes are not Associated with Gestational Weight Trajectory.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets