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.
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The Center for Genomic Medicine (CGM) comprises one of the largest and most vibrant hubs of genomic medicine research in the world. The CGM includes 46 faculty collaborating to define the ‘genomic medicine cycle’ – which envisages a genomics community seeking to advance research from basic genomics research to ultimately using genome information for diagnostics and targeted therapeutics. All of our investigators are faculty at Harvard Medical School, and many members of our community are also investigators at the Broad Institute of Harvard and MIT.
