Global Biobank analyses provide lessons for developing polygenic risk scores across diverse cohorts

• DOI: 10.1016/j.xgen.2022.100241
• Publication Date: 2023-01-05T04:33:33Z
• Authors: Ying Wang; Shinichi Namba; Esteban Lopera; Sini Kerminen; Kristin Tsuo; Kristi Läll; Masahiro Kanai; Wei Zhou; Kuan-Han Wu; Marie-Julie Favé; Laxmi Bhatta; Philip Awadalla; Ben Brumpton; Patrick Deelen; Kristian Hveem; Valeria Lo Faro; Reedik Mägi; Yoshinori Murakami; Serena Sanna; Jordan W. Smoller; Jasmina Uzunovic; Brooke N. Wolford; Cristen Willer; Eric R. Gamazon; Nancy J. Cox; Ida Surakka; Yukinori Okada; Alicia R. Martin; Jibril Hirbo; Wei Zhou; Masahiro Kanai; Kuan-Han H. Wu; Humaira Rasheed; Kristin Tsuo; Jibril B. Hirbo; Ying Wang; Arjun Bhattacharya; Huiling Zhao; Shinichi Namba; Ida Surakka; Brooke N. Wolford; Valeria Lo Faro; Esteban A. Lopera...; Kristi Läll; Marie-Julie Favé; Sinéad B. Chapman; Juha Karjalainen; Mitja Kurki; Maasha Mutaamba; Juulia J. Partanen; Ben M. Brumpton; Sameer Chavan; Tzu-Ting Chen; Michelle Daya; Yi Ding; Yen-Chen A. Feng; Christopher R. Gi...; Sarah E. Graham; Whitney E. Hornsby; Nathan Ingold; Ruth Johnson; Triin Laisk; Kuang Lin; Jun Lv; Iona Y. Millwood; Priit Palta; Anita Pandit; Michael H. Preuss; Unnur Thorsteinsd...; Jasmina Uzunovic; Matthew Zawistowski; Xue Zhong; Archie Campbell; Kristy Crooks; Geertruida H. de ...; Nicholas J. Douville; Sarah Finer; Lars G. Fritsche; Christopher J. Gr...; Yu Guo; Karen A. Hunt; Takahiro Konuma; Riccardo E. Marioni; Jansonius Nomdo; Snehal Patil; Nicholas Rafaels; Anne Richmond; Jonathan A. Shortt; Peter Straub; Ran Tao; Brett Vanderwerff; Kathleen C. Barnes; Marike Boezen; Zhengming Chen; Chia-Yen Chen; Judy Cho; George Davey Smith; Hilary K. Finucane; Lude Franke; Eric R. Gamazon; Andrea Ganna; Tom R. Gaunt; Tian Ge; Hailiang Huang; Jennifer Huffman; Jukka T. Koskela; Clara Lajonchere; Matthew H. Law; Liming Li; Cecilia M. Lindgren; Ruth J.F. Loos; Stuart MacGregor; Koichi Matsuda; Catherine M. Olsen; David J. Porteous; Jordan A. Shavit; Harold Snieder; Richard C. Trembath; Judith M. Vonk; David Whiteman; Stephen J. Wicks; Cisca Wijmenga; John Wright; Jie Zheng; Xiang Zhou; Philip Awadalla; Michael Boehnke; Nancy J. Cox; Daniel H. Geschwind; Caroline Hayward; Kristian Hveem; Eimear E. Kenny; Yen-Feng Lin; Reedik Mägi; Hilary C. Martin; Sarah E. Medland; Yukinori Okada; Aarno V. Palotie; Bogdan Pasaniuc; Serena Sanna; Jordan W. Smoller; Kari Stefansson; David A. van Heel; Robin G. Walters; Sebastian Zöllner; Alicia R. Martin; Cristen J. Willer; Mark J. Daly; Benjamin M. Neale
• Keywords: Linkage Disequilibrium; Genome-wide Association Study; Genetic Association

Polygenic risk scores (PRSs) have been widely explored in precision medicine. However, few studies thoroughly investigated their best practices global populations across different diseases. We here utilized data from Global Biobank Meta-analysis Initiative (GBMI) to explore methodological considerations and PRS performance 9 biobanks for 14 disease endpoints. Specifically, we constructed PRSs using pruning thresholding (P + T) PRS-continuous shrinkage (CS). For both methods, a European-based linkage disequilibrium (LD) reference panel resulted comparable or higher prediction accuracy compared with several other non-European-based panels. PRS-CS overall outperformed the classic P T method, especially endpoints SNP-based heritability. Notably, is heterogeneous endpoints, biobanks, ancestries, asthma, which has known variation prevalence populations. Overall, provide lessons construction, evaluation, interpretation GBMI resources highlight importance of biobank-scale genomics era.