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Unappreciated subcontinental admixture in Europeans and European Americans and implications for genetic epidemiology studies.
Gouveia, Mateus H; Bentley, Amy R; Leal, Thiago P; Tarazona-Santos, Eduardo; Bustamante, Carlos D; Adeyemo, Adebowale A; Rotimi, Charles N; Shriner, Daniel.
Afiliación
  • Gouveia MH; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Bentley AR; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Leal TP; Department of Genomic Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44197, USA.
  • Tarazona-Santos E; Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, 31270-910, Brazil.
  • Bustamante CD; Center for Computational, Evolutionary and Human Genomics (CEHG), Stanford University, Stanford, CA, 94305, USA.
  • Adeyemo AA; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Rotimi CN; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA. rotimic@mail.nih.gov.
  • Shriner D; Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA. shrinerda@mail.nih.gov.
Nat Commun ; 14(1): 6802, 2023 11 07.
Article en En | MEDLINE | ID: mdl-37935687
European-ancestry populations are recognized as stratified but not as admixed, implying that residual confounding by locus-specific ancestry can affect studies of association, polygenic adaptation, and polygenic risk scores. We integrate individual-level genome-wide data from ~19,000 European-ancestry individuals across 79 European populations and five European American cohorts. We generate a new reference panel that captures ancestral diversity missed by both the 1000 Genomes and Human Genome Diversity Projects. Both Europeans and European Americans are admixed at the subcontinental level, with admixture dates differing among subgroups of European Americans. After adjustment for both genome-wide and locus-specific ancestry, associations between a highly differentiated variant in LCT (rs4988235) and height or LDL-cholesterol were confirmed to be false positives whereas the association between LCT and body mass index was genuine. We provide formal evidence of subcontinental admixture in individuals with European ancestry, which, if not properly accounted for, can produce spurious results in genetic epidemiology studies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Genética de Población / Pueblo Europeo Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Genética de Población / Pueblo Europeo Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido