Genome-wide risk prediction of common diseases across ancestries in one million people

• DOI: 10.1016/j.xgen.2022.100118
• Publication Date: 2022-04-13T10:36:26Z
• Authors: Nina Mars; Sini Kerminen; Yen-Chen A. Feng; Masahiro Kanai; Kristi Läll; Laurent F. Thomas; Anne Heidi Skogholt; Pietro della Brio...; Benjamin M. Neale; Jordan W. Smoller; Maiken E. Gabrielsen; Kristian Hveem; Reedik Mägi; Koichi Matsuda; Yukinori Okada; Matti Pirinen; Aarno Palotie; Andrea Ganna; Alicia R. Martin; Samuli Ripatti
• Keywords: Genome-wide Association Study; Transferability; Genetic genealogy

Polygenic risk scores (PRS) measure genetic disease susceptibility by combining effects across the genome. For coronary artery (CAD), type 2 diabetes (T2D), and breast prostate cancer, we performed cross-ancestry evaluation of genome-wide PRSs in six biobanks Europe, United States, Asia. We studied transferability these highly polygenic, global ancestries, within European populations with different health-care systems, local population substructures a isolate. All four had similar accuracy Asian populations, poorer smaller group individuals African ancestry. The effect sizes ancestry, early- late-settlement regions recent bottlenecks Finland. Comparing to containing number variants, generally displayed higher better ancestries. Our findings indicate that investigated, current polygenic for common diseases have potential clinical utility settings but ancestry is currently much lower.