Genetic analyses of diverse populations improves discovery for complex traits

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Creator
  • Wojcik, G.L.
    • Other Affiliation: Stanford University
  • Graff, M.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Nishimura, K.K.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Tao, R.
    • Other Affiliation: Vanderbilt University Medical Center
  • Haessler, J.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Gignoux, C.R.
    • Other Affiliation: Stanford University
  • Highland, H.M.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Patel, Y.M.
    • Other Affiliation: University of Southern California
  • Sorokin, E.P.
    • Other Affiliation: Stanford University
  • Avery, C.L.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Belbin, G.M.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Bien, S.A.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Cheng, I.
    • Other Affiliation: University of California San Francisco
  • Cullina, S.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Hodonsky, C.J.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Hu, Y.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Huckins, L.M.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Jeff, J.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Justice, A.E.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Kocarnik, J.M.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Lim, U.
    • Other Affiliation: University of Hawaii Cancer Center
  • Lin, B.M.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Lu, Y.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Nelson, S.C.
    • Other Affiliation: University of Washington
  • Park, S.-S.L.
    • Other Affiliation: University of Southern California
  • Poisner, H.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Preuss, M.H.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Richard, M.A.
    • Other Affiliation: The University of Texas Health Science Center
  • Schurmann, C.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Setiawan, V.W.
    • Other Affiliation: University of Southern California
  • Sockell, A.
    • Other Affiliation: Stanford University
  • Vahi, K.
    • Other Affiliation: University of Southern California
  • Verbanck, M.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Vishnu, A.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Walker, R.W.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Young, K.L.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Zubair, N.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Acuña-Alonso, V.
    • Other Affiliation: Escuela Nacional de Antropologia e Historia
  • Ambite, J.L.
    • Other Affiliation: University of Southern California
  • Barnes, K.C.
    • Other Affiliation: University of Colorado Anschutz Medical Campus
  • Boerwinkle, E.
    • Other Affiliation: The University of Texas Health Science Center
  • Bottinger, E.P.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Bustamante, C.D.
    • Other Affiliation: Stanford University
  • Caberto, C.
    • Other Affiliation: University of Hawaii Cancer Center
  • Canizales-Quinteros, S.
    • Other Affiliation: Instituto Nacional de Medicina Genómica
  • Conomos, M.P.
    • Other Affiliation: University of Washington
  • Deelman, E.
    • Other Affiliation: University of Southern California
  • Do, R.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Doheny, K.
    • Other Affiliation: Johns Hopkins University
  • Fernández-Rhodes, L.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Fornage, M.
    • Other Affiliation: The University of Texas Health Science Center
  • Hailu, B.
    • Other Affiliation: NIH National Institute on Minority Health and Health Disparities
  • Heiss, G.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Henn, B.M.
    • Other Affiliation: University of California Davis
  • Hindorff, L.A.
    • Other Affiliation: NIH National Human Genome Research Institute
  • Jackson, R.D.
    • Other Affiliation: Ohio State Medical Center
  • Laurie, C.A.
    • Other Affiliation: University of Washington
  • Laurie, C.C.
    • Other Affiliation: University of Washington
  • Li, Y.
    • Other Affiliation: University of California San Francisco
  • Lin, D.-Y.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Moreno-Estrada, A.
    • Other Affiliation: National Laboratory of Genomics for Biodiversity (UGA-LANGEBIO)
  • Nadkarni, G.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Norman, P.J.
    • Other Affiliation: University of Colorado Anschutz Medical Campus
  • Pooler, Lareall C.
    • Other Affiliation: University of Southern California
  • Reiner, A.P.
    • Other Affiliation: University of Washington
  • Romm, J.
    • Other Affiliation: Johns Hopkins University
  • Sabatti, C.
    • Other Affiliation: Stanford University
  • Sandoval, K.
    • Other Affiliation: National Laboratory of Genomics for Biodiversity (UGA-LANGEBIO)
  • Sheng, X.
    • Other Affiliation: University of Southern California
  • Stahl, E.A.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Stram, D.O.
    • Other Affiliation: University of Southern California
  • Thornton, T.A.
    • Other Affiliation: University of Washington
  • Wassel, C.L.
    • Other Affiliation: University of Vermont
  • Wilkens, L.R.
    • Other Affiliation: University of Hawaii Cancer Center
  • Winkler, C.A.
    • Other Affiliation: Frederick National Laboratory
  • Yoneyama, S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Buyske, S.
    • Other Affiliation: Rutgers University
  • Haiman, C.A.
    • Other Affiliation: University of Southern California
  • Kooperberg, C.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Le Marchand, L.
    • Other Affiliation: University of Hawaii Cancer Center
  • Loos, R.J.F.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Matise, T.C.
    • Other Affiliation: Rutgers University
  • North, K.E.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Peters, U.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Kenny, E.E.
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • Carlson, C.S.
    • Other Affiliation: Fred Hutchinson Cancer Research Center
Abstract
  • Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry1–3. In light of the differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and healthcare disparities. Critical variants may be missed if they have a low frequency or are completely absent in European populations, especially as the field shifts its attention towards rare variants, which are more likely to be population-specific4–10. Additionally, effect sizes and their derived risk prediction scores derived in one population may not accurately extrapolate to other populations11,12. Here we demonstrate the value of diverse, multi-ethnic participants in large-scale genomic studies. The Population Architecture using Genomics and Epidemiology (PAGE) study conducted a GWAS of 26 clinical and behavioural phenotypes in 49,839 non-European individuals. Using strategies tailored for analysis of multi-ethnic and admixed populations, we describe a framework for analysing diverse populations, identify 27 novel loci and 38 secondary signals at known loci, as well as replicate 1,444 GWAS catalogue associations across these traits. Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts and insights into clinical implications. In the United States—where minority populations have a disproportionately higher burden of chronic conditions13—the lack of representation of diverse populations in genetic research will result in inequitable access to precision medicine for those with the highest burden of disease. We strongly advocate for continued, large genome-wide efforts in diverse populations to maximize genetic discovery and reduce health disparities. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
Date of publication
DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Nature
Journal volume
  • 570
Journal issue
  • 7762
Page start
  • 514
Page end
  • 518
Language
  • English
ISSN
  • 0028-0836
Publisher
  • Nature Publishing Group

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