Daniel Hui, Scott Dudek, Krzysztof Kiryluk, Theresa L Walunas, Iftikhar J Kullo, Wei-Qi Wei, Hemant K Tiwari, Josh F Peterson, Wendy K Chung, Brittney Davis, Atlas Khan, Leah Kottyan, Nita A Limdi, Qiping Feng, Megan J Puckelwartz, Chunhua Weng, Johanna L Smith, Elizabeth W Karlson, Regeneron Genetics Center, Gail P Jarvik, Marylyn D Ritchie
Apart from ancestry, personal or environmental covariates may contribute to differences in polygenic score (PGS) performance. We analyzed effects of covariate stratification and interaction on body mass index (BMI) PGS (PGS BMI ) across four cohorts of European (N=491,111) and African (N=21,612) ancestry. Stratifying on binary covariates and quintiles for continuous covariates, 18/62 covariates had significant and replicable R 2 differences among strata. Covariates with the largest differences included age, sex, blood lipids, physical activity, and alcohol consumption, with R 2 being nearly double between best and worst performing quintiles for certain covariates...
April 10, 2024: medRxiv