Identification of Genetic Variation Influencing Metformin Response in a Multi-Ancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP)
Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not replicated in the Diabetes Prevention Program (DPP). To assess pharmacogenetic interactions in pre-diabetes, CGM investigator Jose Florez and colleagues conducted a GWAS in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (n=876) and placebo (n=887) arms. Multiple linear regression assessed association with one-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal components. The investigators identified four genome-wide significant variants after correcting for correlated traits (p<9×10-9). These novel ethnic-specific associations require further investigation but may have implications for tailored therapy.