Identification of Genetic Variation Influencing Metformin Response in a Multi-Ancestry Genome-Wide Association Study in the Diabetes Prevention Program (DPP)
| Autor: | Josephine H, Li, James A, Perry, Kathleen A, Jablonski, Shylaja, Srinivasan, Ling, Chen, Jennifer N, Todd, Maegan, Harden, Josep M, Mercader, Qing, Pan, Adem Y, Dawed, Sook Wah, Yee, Ewan R, Pearson, Kathleen M, Giacomini, Ayush, Giri, Adriana M, Hung, Shujie, Xiao, L Keoki, Williams, Paul W, Franks, Robert L, Hanson, Steven E, Kahn, William C, Knowler, Toni I, Pollin, Jose C, Florez |
|---|---|
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Diabetes. |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | 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, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in metformin (MET, n=876) and placebo (PBO, 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. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes incidence. We identified four genome-wide significant variants after correcting for correlated traits (p |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|