Dataset Information

Searching and visualizing genetic associations of pregnancy traits by using GnuMoM2b.

ABSTRACT: Adverse pregnancy outcomes (APOs) are major risk factors for women's health during pregnancy and even in the years after pregnancy. Due to the heterogeneity of APOs, only few genetic associations have been identified. In this report, we conducted genome-wide association studies (GWASs) of 479 traits that are possibly related to APOs using a large and racially diverse study, Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). To display extensive results, we developed a web-based tool GnuMoM2b (https://gnumom2b.cumcobgyn.org/) for searching, visualizing, and sharing results from a GWAS of 479 pregnancy traits as well as phenome-wide association studies of more than 17 million single nucleotide polymorphisms. The genetic results from 3 ancestries (Europeans, Africans, and Admixed Americans) and meta-analyses are populated in GnuMoM2b. In conclusion, GnuMoM2b is a valuable resource for extraction of pregnancy-related genetic results and shows the potential to facilitate meaningful discoveries.

SUBMITTER: Yan Q

PROVIDER: S-EPMC10691790 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Searching and visualizing genetic associations of pregnancy traits by using GnuMoM2b.

Yan Qi Q Guerrero Rafael F RF Khan Raiyan R RR Surujnarine Andy A AA Wapner Ronald J RJ Hahn Matthew W MW Raja Anita A Salleb-Aouissi Ansaf A Grobman William A WA Simhan Hyagriv H Blue Nathan R NR Silver Robert R Chung Judith H JH Reddy Uma M UM Radivojac Predrag P Pe'er Itsik I Haas David M DM

Genetics 20231001 2

Adverse pregnancy outcomes (APOs) are major risk factors for women's health during pregnancy and even in the years after pregnancy. Due to the heterogeneity of APOs, only few genetic associations have been identified. In this report, we conducted genome-wide association studies (GWASs) of 479 traits that are possibly related to APOs using a large and racially diverse study, Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). To display extensive results, we developed a web- ...[more]

PMID: 37602697

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Project description:Aims/hypothesisOur study aimed to integrate maternal metabolic and genetic data related to insulin sensitivity during pregnancy to provide novel insights into mechanisms underlying pregnancy-induced insulin resistance.MethodsFasting and 1 h serum samples were collected from women in the Hyperglycemia and Adverse Pregnancy Outcome study who underwent an OGTT at ∼28 weeks' gestation. We obtained targeted and non-targeted metabolomics and genome-wide association data from 1600 and 4528 mothers, respectively, in four ancestry groups (Northern European, Afro-Caribbean, Mexican American and Thai); 1412 of the women had both metabolomics and genome-wide association data. Insulin sensitivity was calculated using a modified insulin sensitivity index that included fasting and 1 h glucose and C-peptide levels after a 75 g glucose load.ResultsPer-metabolite and network analyses across the four ancestries identified numerous metabolites associated with maternal insulin sensitivity before and 1 h after a glucose load, ranging from amino acids and carbohydrates to fatty acids and lipids. Genome-wide association analyses identified 12 genetic variants in the glucokinase regulatory protein gene locus that were significantly associated with maternal insulin sensitivity, including a common functional missense mutation, rs1260326 (β = -0.2004, p = 4.67 × 10-12 in a meta-analysis across the four ancestries). This SNP was also significantly associated with multiple fasting and 1 h metabolites during pregnancy, including fasting and 1 h triacylglycerols and 2-hydroxybutyrate and 1 h lactate, 2-ketoleucine/ketoisoleucine and palmitoleic acid. Mediation analysis suggested that 1 h palmitoleic acid contributes, in part, to the association of rs1260326 with maternal insulin sensitivity, explaining 13.7% (95% CI 4.0%, 23.3%) of the total effect.Conclusions/interpretationThe present study demonstrates commonalities between metabolites and genetic variants associated with insulin sensitivity in the gravid and non-gravid states and provides insights into mechanisms underlying pregnancy-induced insulin resistance. Graphical abstract.

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Searching and visualizing genetic associations of pregnancy traits by using GnuMoM2b.

Publications

Searching and visualizing genetic associations of pregnancy traits by using GnuMoM2b.

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