Genome-wide risk prediction of common diseases across ancestries in one million people
Nina Mars,
Sini Kerminen,
Yen-Chen A. Feng,
Masahiro Kanai,
Kristi Läll,
Laurent F. Thomas,
Anne Heidi Skogholt,
Pietro della Briotta Parolo,
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
Affiliations
Nina Mars
Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Biomedicum 2U, Tukholmankatu 8, 00290 Helsinki, Finland
Sini Kerminen
Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Biomedicum 2U, Tukholmankatu 8, 00290 Helsinki, Finland
Yen-Chen A. Feng
Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
Masahiro Kanai
Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
Kristi Läll
Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
Laurent F. Thomas
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway; BioCore - Bioinformatics Core Facility, Norwegian University of Science and Technology, Trondheim, Norway
Anne Heidi Skogholt
K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway
Pietro della Briotta Parolo
Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Biomedicum 2U, Tukholmankatu 8, 00290 Helsinki, Finland
Benjamin M. Neale
Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA
Jordan W. Smoller
Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA
Maiken E. Gabrielsen
K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway; HUNT Research Center, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
Kristian Hveem
K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health, Norwegian University of Science and Technology, Trondheim, Norway
Reedik Mägi
Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
Koichi Matsuda
Department of Computational Biology and Medical Sciences, Graduate school of Frontier Sciences, the University of Tokyo, Tokyo, Japan
Yukinori Okada
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan; Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan; Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan
Matti Pirinen
Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Biomedicum 2U, Tukholmankatu 8, 00290 Helsinki, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland; Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland
Aarno Palotie
Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Biomedicum 2U, Tukholmankatu 8, 00290 Helsinki, Finland; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
Andrea Ganna
Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Biomedicum 2U, Tukholmankatu 8, 00290 Helsinki, Finland; Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA
Alicia R. Martin
Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
Samuli Ripatti
Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Biomedicum 2U, Tukholmankatu 8, 00290 Helsinki, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Corresponding author
Summary: Polygenic risk scores (PRS) measure genetic disease susceptibility by combining risk effects across the genome. For coronary artery disease (CAD), type 2 diabetes (T2D), and breast and prostate cancer, we performed cross-ancestry evaluation of genome-wide PRSs in six biobanks in Europe, the United States, and Asia. We studied transferability of these highly polygenic, genome-wide PRSs across global ancestries, within European populations with different health-care systems, and local population substructures in a population isolate. All four PRSs had similar accuracy across European and Asian populations, with poorer transferability in the smaller group of individuals of African ancestry. The PRSs had highly similar effect sizes in different populations of European ancestry, and in early- and late-settlement regions with different recent population bottlenecks in Finland. Comparing genome-wide PRSs to PRSs containing a smaller number of variants, the highly polygenic, genome-wide PRSs generally displayed higher effect sizes and better transferability across global ancestries. Our findings indicate that in the populations investigated, the current genome-wide polygenic scores for common diseases have potential for clinical utility within different health-care settings for individuals of European ancestry, but that the utility in individuals of African ancestry is currently much lower.
