Dataset Information

The transcriptome-wide association search for genes and genetic variants which associate with BMI and gestational weight gain in women with type 1 diabetes.

ABSTRACT:

Background

Clinical data suggest that BMI and gestational weight gain (GWG) are strongly interconnected phenotypes; however, the genetic basis of the latter is rather unclear. Here we aim to find genes and genetic variants which influence BMI and/or GWG.

Methods

We have genotyped 316 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays. The GIANT, ARIC and T2D-GENES summary statistics were used for TWAS (performed with PrediXcan) in adipose tissue. Next, the analysis of association of imputed expression with BMI in the general and diabetic cohorts (Analysis 1 and 2) or GWG (Analysis 3 and 4) was performed, followed by variant association analysis (1 Mb around identified loci) with the mentioned phenotypes.

Results

In Analysis 1 we have found 175 BMI associated genes and 19 variants (p?-4) which influenced GWG, with the strongest association for rs11465293 in CCL24 (p?=?3.18E-06). Analysis 2, with diabetes included in the model, led to discovery of 1812 BMI associated loci and 207 variants (p?-4) influencing GWG, with the strongest association for rs9690213 in PODXL (p?=?9.86E-07). In Analysis 3, among 648 GWG associated loci, 2091 variants were associated with BMI (FDR?ConclusionsHere, we have shown that loci influencing BMI might have an impact on GWG and GWG associated loci might influence BMI, both in the general and T1DM cohorts. The results suggest that both phenotypes are related to insulin signaling, glucose homeostasis, mitochondrial metabolism, ubiquitinoylation and inflammatory responses.

SUBMITTER: Ludwig-Slomczynska AH

PROVIDER: S-EPMC7818927 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The transcriptome-wide association search for genes and genetic variants which associate with BMI and gestational weight gain in women with type 1 diabetes.

Ludwig-Słomczyńska Agnieszka H AH Seweryn Michał T MT Kapusta Przemysław P Pitera Ewelina E Mantaj Urszula U Cyganek Katarzyna K Gutaj Paweł P Dobrucka Łucja Ł Wender-Ożegowska Ewa E Małecki Maciej T MT Wołkow Paweł P PP

Molecular medicine (Cambridge, Mass.) 20210120 1

<h4>Background</h4>Clinical data suggest that BMI and gestational weight gain (GWG) are strongly interconnected phenotypes; however, the genetic basis of the latter is rather unclear. Here we aim to find genes and genetic variants which influence BMI and/or GWG.<h4>Methods</h4>We have genotyped 316 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays. The GIANT, ARIC and T2D-GENES summary statistics were used for TWAS (performed with PrediXcan) in adipose tissue. Next, the a ...[more]

PMID: 33472578

Similar Datasets

Project description:IntroductionDespite the important clinical significance, limited data on the joint contribution of prepregnancy body mass index (BMI) and gestational weight gain (GWG) to preeclampsia, the second leading cause of maternal mortality worldwide. This study aimed to estimate the risk of preeclampsia by GWG among women with varied prepregnancy BMI.MethodsWe conducted a retrospective cohort study using data of 117 738 singleton pregnant women aged 18-49 years from 150 maternity hospitals in China between 2015 and 2018. GWG was calculated as the measured weight at the time of preeclampsia assessment minus prepregnancy weight; GWG velocity was calculated as the GWG divided by the gestational age at weighing. The non-linear associations of GWG with preeclampsia were examined by restricted cubic spline regression analysis according to prepregnancy BMI. The association of the GWG categories with preeclampsia was further examined by performing robust Poisson regression stratified by the prepregnancy BMI categories.ResultsAmong participants, 2426 (2.06%) were diagnosed with preeclampsia. Compared to women with normal BMI, those who were overweight and obese had 1.92- fold (95%CI, 1.73-2.14) and 5.06- fold (95%CI, 4.43-5.78) increased risks for preeclampsia, respectively. The association of GWG velocity with preeclampsia was presented as a J-shaped curve with the varied inflexion point (where the rate of preeclampsia was 2%), which was 0.54, 0.38, and 0.25 kg/week in women with normal BMI, overweight, and obesity, respectively; a steep risk rise was observed along with GWG velocity beyond the inflexion points. The overall adjusted relative risk for preeclampsia was calculated among women with the different GWG categories of GWG.ConclusionsThe findings highlight that high prepregnancy BMI and exceed GWG contributed to increased risk of preeclampsia with a superimposed effect and underscore the need to optimize the recommendations for GWG for women with different prepregnancy BMI.

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:BackgroundPhthalates are endocrine disrupting chemicals that may influence weight status; however, few studies have considered weight gain during pregnancy and subsequent long-term weight changes in women.ObjectiveTo determine associations of prenatal phthalate exposure with maternal weight during pregnancy and through up to seven years post-delivery.MethodsWe analyzed 15 urinary phthalate biomarker concentrations during the 2nd and 3rd trimesters among 874 pregnant women enrolled in the Programming Research in Obesity, Growth Environment and Social Stress Study in Mexico City. We examined three time-specific maternal weight outcomes: gestational weight gain (between 2nd and 3rd trimesters), short-term weight (between 3rd trimester and 12 months post-delivery), and long-term weight (between 18 months and 6-7 years post-delivery). We used Bayesian Kernel Machine Regression (BKMR) to estimate associations for the total phthalate mixture, as well as multivariable linear mixed models for individual phthalate biomarkers.ResultsAs a mixture, 2nd trimester urinary phthalate biomarker concentrations were associated with somewhat lower gestational weight gain between the 2nd and 3rd trimesters (interquartile range, IQR, difference: -0.07 standard deviations, SD; 95% credible interval, CrI: -0.20, 0.06); multivariable regression and BKMR models indicated that this inverse association was primarily driven by mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP). Prenatal (2nd and 3rd trimesters) urinary phthalate mixture concentrations were positively associated with maternal weight change through 12 months postpartum (IQR difference: 0.11 SD; 95% CrI: 0.00, 0.23); these associations persisted from 18 months to 6-7 years follow-up (IQR difference: 0.07 SD; 95% CrI: 0.04, 0.10). Postpartum weight changes were associated with mono-3-carboxypropyl phthalate (MCPP) and MECPTP.ConclusionsPrenatal phthalate exposure was inversely associated with gestational weight gain and positively associated with long-term changes in maternal weight. Further investigation is required to understand how phthalates may influence body composition and whether they contribute to the development of obesity and other cardiometabolic diseases in women.

Dataset Information

The transcriptome-wide association search for genes and genetic variants which associate with BMI and gestational weight gain in women with type 1 diabetes.

Background

Methods

Results

Publications

The transcriptome-wide association search for genes and genetic variants which associate with BMI and gestational weight gain in women with type 1 diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets