# Genome, Metabolome, Ancestry and Diabetes Health Disparity

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2021 · $618,591

## Abstract

ABSTRACT
Our genome-metabolome investigations of type 2 diabetes (T2D) and the associated cardiometabolic (CM)
complications are one of the high-priority research areas for the NIH to understand the causes of disparities in health
in underserved populations of the US. T2D prevalence is projected to increase from 10% currently to 33% by the
year 2050 in the US. South Asians (SAs) are a rapidly growing ethnic minority group, and have a well-documented
high predisposition to T2D and cardiovascular diseases. Although it is well known that genetic and environmental
factors influence T2D, the underlying mechanisms are poorly characterized in SAs.
 Recent studies performed in European populations have identified genetic factors influencing metabolite
concentrations in patients with a wide spectrum of cardiometabolic diseases using metabolome-wide/genome-wide
technologies. However, no such study has ever been performed in any population from India despite the fact that
about one in four people in the global population are part of the SA population. Unlike conventional genome-wide
association studies (GWAS), the metabolome GWAS (mGWAS) has higher statistical power to capture common
genetic variation. Given the promise of the genome-metabolome approaches in elucidating underlying genetic causes
for disease, such investigations in other non-white ethnic cohorts are critical to achieve advances in precision
medicine. Essentially, such studies will help characterize unique metabolites linked with the “non-
obese/metabolically-obese” phenotype of T2D in SAs and others.
 Therefore in this investigation, using existing resources of already collected family and population-based
samples (n=5,250) from the Asian Indian Diabetic Heart Study (AIDHS), our strategy is to cost-effectively integrate
phenotypic, metabolomic, and genomic data to investigate the underlying genetic mechanisms regulating T2D
pathophysiology. We propose these three specific aims for this proposal: AIM 1: Generate global (untargeted)
metabolome profiles to identify and characterize small heritable molecules genetically correlated with T2D and related
cardiometabolic traits using GCxGC-MS; AIM 2: Perform mGWAS to identify mQTLs and variants simultaneously
associated with T2D, metabolites, and other traits; Replicate association of the top mQTL variants and ~15-20 of most
significant metabolites in additional independent SA samples; AIM 3: Determine differences and similarities of putative
biomarkers for T2D by performing look-up analysis in US multiethnic families, and perform preliminary functional
characterization of a few of the most interesting mQTL loci by using zebrafish and knockout mouse models.
OVERALL IMPACT: No comparable study has ever been undertaken in people of Asian Indian descent. With our
outstanding team, a unique high-risk homogenous Sikh population, and cost-effective utilization of existing resources,
our project has high potential to identify novel biomarkers of therapeuti...

## Key facts

- **NIH application ID:** 10241268
- **Project number:** 5R01DK118427-03
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** RAVINDRANATH DUGGIRALA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $618,591
- **Award type:** 5
- **Project period:** 2019-09-05 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241268

## Citation

> US National Institutes of Health, RePORTER application 10241268, Genome, Metabolome, Ancestry and Diabetes Health Disparity (5R01DK118427-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241268. Licensed CC0.

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