PLoS Med. 2026 Apr 23;23(4):e1005039. doi: 10.1371/journal.pmed.1005039. eCollection 2026 Apr.
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.
PMID:42024661 | DOI:10.1371/journal.pmed.1005039