# Influence of genetic variation, genetic ancestry, and obesity on gestational diabetes mellitus risk

> **NIH NIH K01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $140,257

## Abstract

PROJECT SUMMARY/ABSTRACT
Gestational diabetes mellitus (GDM), is among the most common pregnancy complications in the US. Shared
pathophysiology with type-2 diabetes (T2D), evidence of familial aggregation, and evidence of racial disparity
all support a role for genetic predisposition. Asian American (AAM) and Hispanic American (HA) women have
lower prevalence of obesity on average than African American (AA) women, yet have higher GDM prevalence:
10.2%, 6.8%, 4.5% and 4.4% in AAM, HA, European American (EA) and AA women, respectively. Current
studies are limited to candidate gene investigations with most investigating five to ten known T2D loci and only
one genome-wide association study (GWAS) (468 cases; 1242 controls), in a South-Korean population. AAMs
and HAs are the fastest growing populations in the US. Despite evident racial disparity suggesting a genetic
etiology, no study has evaluated whether this is in part is rooted in differences associated with genetic
ancestry. The overall goals of this proposal are to expand comprehensive genetic investigations of GDM and
related traits by leveraging electronic health records (EHR) and bio-repositories to better understand the
etiology which may inform personalized strategies for screening and prevention. We aim to develop, refine and
validate reproducible and portable bioinformatics-algorithms to identity GDM cases and controls using de-
identified EHR data at Vanderbilt. We will evaluate whether reported race/ethnicity modifies the association
between maternal BMI and GDM in the Vanderbilt EHR database, the synthetic derivative (SD) (>8000 cases;
Aim 1.1). In approximately 2,200 cases and 4,400 controls with genetic data, we will perform a Mendelian
randomization study to test whether genetic instruments of central obesity (waist to hip ratio) or overall obesity
(BMI) are more strongly associated with GDM (Aim 1.2). We will perform the first two-stage trans-ethnic GWAS
of GDM in the US in EA, AA, HA, and AAM women from the SD and replicate associated variants (P < 1x10-6)
in over 1000 GDM cases and many controls from the UK Biobank and Mount Sinai BioME EHR-linked bio-
repository (Aim 2.1). By integrating GWAS data and expression quantitative trait loci (eQTL) data from various
tissues with methods such as S-PrediXcan, we will prioritize candidate causal genes for GDM (Aim 2.2).
Finally, we will explore whether genetically inferred Asian/Native American ancestry proportion is associated
with increased risk of GDM (Aim 3.1) and T2D (Aim 3.2) in HAs. The well-tailored mentored training program
supports the stated research aims and provides the candidate with the protected time to gain appropriate
training in areas in which he lacks fully independent expertise, including phenotyping in the EHR setting,
biomedical informatics and knowledge of gestational diabetes and classification of pregnancy outcomes.
Successful completion of this award will facilitate the candidate's development into an independ...

## Key facts

- **NIH application ID:** 10113596
- **Project number:** 5K01DK120631-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Ayush Giri
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $140,257
- **Award type:** 5
- **Project period:** 2020-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10113596

## Citation

> US National Institutes of Health, RePORTER application 10113596, Influence of genetic variation, genetic ancestry, and obesity on gestational diabetes mellitus risk (5K01DK120631-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10113596. Licensed CC0.

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