Global Biobank analyses provide lessons for developing polygenic risk scores across diverse cohorts
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Polygenic risk scores (PRSs) have been widely explored in precision medicine. However, few studies have thoroughly investigated their best practices in global populations across different diseases. We here utilized data from Global Biobank Meta-analysis Initiative (GBMI) to explore methodological considerations and PRS performance in 9 different biobanks for 14 disease endpoints. Specifically, we constructed PRSs using pruning and thresholding (P + T) and PRS-continuous shrinkage (CS). For both methods, using a European-based linkage disequilibrium (LD) reference panel resulted in comparable or higher prediction accuracy compared with several other non-European-based panels. PRS-CS overall outperformed the classic P + T method, especially for endpoints with higher SNP-based heritability. Notably, prediction accuracy is heterogeneous across endpoints, biobanks, and ancestries, especially for asthma, which has known variation in disease prevalence across populations. Overall, we provide lessons for PRS construction, evaluation, and interpretation using GBMI resources and highlight the importance of best practices for PRS in the biobank-scale genomics era.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 100241 |
| Tidsskrift | Cell Genomics |
| Vol/bind | 3 |
| Udgave nummer | 1 |
| Antal sider | 18 |
| ISSN | 2666-979x |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
A.R.M. is funded by K99/R00MH117229 . E.L. is funded by the Colciencias fellowship ed.783. S.N. was supported by Takeda Science Foundation . Y.O. was supported by JSPS KAKENHI ( 22H00476 ) and AMED ( JP21gm4010006 , JP22km0405211 , JP22ek0410075 , JP22km0405217 , and JP22ek0109594 ); JST Moonshot R&D ( JPMJMS2021 and JPMJMS2024 ); Takeda Science Foundation ; and Bioinformatics Initiative of Osaka University Graduate School of Medicine, Osaka University . E.R.G. is supported by NIH awards R35HG010718 , R01HG011138 , and R01GM140287 and NIH /NIA AG068026 . V.L.F. was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 675033 (EGRET plus). L.B. and B.B. receive support from the K.G. Jebsen Center for Genetic Epidemiology funded by Stiftelsen Kristian Gerhard Jebsen; the Faculty of Medicine and Health Sciences, NTNU; the Liaison Committee for education, research and innovation in Central Norway; and the Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU. K.L. and R.M. were supported by the Estonian Research Council grant PUT ( PRG687 ) and by INTERVENE. This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 101016775 . W.Z. was supported by the NHGRI of the NIH under award number T32HG010464 . The work of the contributing biobanks was supported by numerous grants from governmental and charitable bodies ( Data S1 ).
Funding Information:
A.R.M. is funded by K99/R00MH117229. E.L. is funded by the Colciencias fellowship ed.783. S.N. was supported by Takeda Science Foundation. Y.O. was supported by JSPS KAKENHI (22H00476) and AMED (JP21gm4010006, JP22km0405211, JP22ek0410075, JP22km0405217, and JP22ek0109594); JST Moonshot R&D (JPMJMS2021 and JPMJMS2024); Takeda Science Foundation; and Bioinformatics Initiative of Osaka University Graduate School of Medicine, Osaka University. E.R.G. is supported by NIH awards R35HG010718, R01HG011138, and R01GM140287 and NIH/NIA AG068026. V.L.F. was supported by the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 675033 (EGRET plus). L.B. and B.B. receive support from the K.G. Jebsen Center for Genetic Epidemiology funded by Stiftelsen Kristian Gerhard Jebsen; the Faculty of Medicine and Health Sciences, NTNU; the Liaison Committee for education, research and innovation in Central Norway; and the Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU. K.L. and R.M. were supported by the Estonian Research Council grant PUT (PRG687) and by INTERVENE. This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement no. 101016775. W.Z. was supported by the NHGRI of the NIH under award number T32HG010464. The work of the contributing biobanks was supported by numerous grants from governmental and charitable bodies (Data S1). Study design, A.R.M. J.H. Y.O. and Y.W.; data collection/contribution, L.B. P.A. B.B. P.D. K.H. R.M. Y.M. S.S. J.U. C.W. N.J.C. I.S. and J.H.; data analysis, Y.W. S.N. E.L. S.K. K.T. K.L. M.K. W.Z. K.-H.W. M.-J.F. L.B. V.L.F. and J.H.; writing, Y.W. S.N. E.L. Y.O. A.R.M. and J.H.; revision, Y.W. S.N. E.L. K.T. W.Z. S.S. J.W.S. B.N.W. C.W. E.R.G. N.J.C. Y.O. A.R.M. and J.H. E.R.G. received an honorarium from the journal Circulation Research of the American Heart Association as a member of the editorial board.
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