School of Medicine Publications
Document Type
Article
Publication Date
4-23-2026
Abstract
Background: Genetic mechanisms that predispose people to type 2 diabetes (T2D) and cardiovascular disease (CVD) remain poorly understood, partly because of a lack of sufficient data on non-European ethnic groups. Extending these evaluations to diverse cohorts is essential for gaining insights into the molecular pathways involved in disease development among human populations. In this study, we aimed to evaluate the genetic connection between the human lipidome and cardiometabolic disorders. We conducted a metabolite genome-wide association study (mGWAS) in a Punjabi population from India, along with multi-layer replication studies using the UK Biobank and other independent European and non-European cohorts.
Methods and findings: We performed mGWAS using 516 lipid metabolites in 3,000 Punjabi Sikh individuals, and validation was performed in 1.13M Europeans and 15K individuals from Asian Indian ancestry using independent cohorts of the UK Biobank, GeneRISK, DIAMANT, PROMIS, and other studies. We identified 609 SNP-metabolite associations representing 236 SNP-metabolite pairs that attained genome-wide significance (p
Conclusions: The mGWAS of Asian Indians offers new insights into the diverse molecular origins of cardiometabolic diseases and suggests potential pathways for innovative treatments. Our findings highlight the need for additional research on human lipidomics to better understand the downstream effects of the genome and its impact on cardiometabolic health.
Recommended Citation
Rout, M., Aston, C. E., Duggirala, R., Goring, H. H., Fiehn, O., & Sanghera, D. K. (2026). Identification of lipid quantitative trait loci linked with cardiometabolic disease in Asian Indians and Europeans: A genome-wide association study and Mendelian randomization. PLoS medicine, 23(4), e1005039. https://doi.org/10.1371/journal.pmed.1005039
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Title
PLoS Medicine
DOI
10.1371/journal.pmed.1005039
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
Copyright: © 2026 Rout et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.