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Causal effects on complex traits are similar for common variants across segments of different continental ancestries within admixed individuals.
Hou, Kangcheng; Ding, Yi; Xu, Ziqi; Wu, Yue; Bhattacharya, Arjun; Mester, Rachel; Belbin, Gillian M; Buyske, Steve; Conti, David V; Darst, Burcu F; Fornage, Myriam; Gignoux, Chris; Guo, Xiuqing; Haiman, Christopher; Kenny, Eimear E; Kim, Michelle; Kooperberg, Charles; Lange, Leslie; Manichaikul, Ani; North, Kari E; Peters, Ulrike; Rasmussen-Torvik, Laura J; Rich, Stephen S; Rotter, Jerome I; Wheeler, Heather E; Wojcik, Genevieve L; Zhou, Ying; Sankararaman, Sriram; Pasaniuc, Bogdan.
Affiliation
  • Hou K; Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA, USA. houkc@ucla.edu.
  • Ding Y; Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA, USA.
  • Xu Z; Department of Computer Science, UCLA, Los Angeles, CA, USA.
  • Wu Y; Department of Computer Science, UCLA, Los Angeles, CA, USA.
  • Bhattacharya A; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Mester R; Graduate Program in Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Belbin GM; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Buyske S; The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Conti DV; Department of Statistics, Rutgers University, Piscataway, NJ, USA.
  • Darst BF; Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Fornage M; Division of Public Health Science, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Gignoux C; Brown Foundation Institute for Molecular Medicine, The University of Texas Health Science Center, Houston, TX, USA.
  • Guo X; Division of Biomedical Informatics and Personalized Medicine, University of Colorado, Denver, CO, USA.
  • Haiman C; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Kenny EE; Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Kim M; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Kooperberg C; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Lange L; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Manichaikul A; Division of Public Health Science, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • North KE; Division of Public Health Science, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Peters U; Department of Medicine, University of Colorado, Aurora, CO, USA.
  • Rasmussen-Torvik LJ; Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
  • Rich SS; Department of Statistics, Rutgers University, Piscataway, NJ, USA.
  • Rotter JI; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Wheeler HE; Division of Public Health Science, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Wojcik GL; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Zhou Y; Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
  • Sankararaman S; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Pasaniuc B; Department of Biology, Loyola University Chicago, Chicago, IL, USA.
Nat Genet ; 55(4): 549-558, 2023 04.
Article in En | MEDLINE | ID: mdl-36941441
ABSTRACT
Individuals of admixed ancestries (for example, African Americans) inherit a mosaic of ancestry segments (local ancestry) originating from multiple continental ancestral populations. This offers the unique opportunity of investigating the similarity of genetic effects on traits across ancestries within the same population. Here we introduce an approach to estimate correlation of causal genetic effects (radmix) across local ancestries and analyze 38 complex traits in African-European admixed individuals (N = 53,001) to observe very high correlations (meta-analysis radmix = 0.95, 95% credible interval 0.93-0.97), much higher than correlation of causal effects across continental ancestries. We replicate our results using regression-based methods from marginal genome-wide association study summary statistics. We also report realistic scenarios where regression-based methods yield inflated heterogeneity-by-ancestry due to ancestry-specific tagging of causal effects, and/or polygenicity. Our results motivate genetic analyses that assume minimal heterogeneity in causal effects by ancestry, with implications for the inclusion of ancestry-diverse individuals in studies.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Multifactorial Inheritance / Genetics, Population Type of study: Systematic_reviews Limits: Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2023 Document type: Article Affiliation country: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Multifactorial Inheritance / Genetics, Population Type of study: Systematic_reviews Limits: Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2023 Document type: Article Affiliation country: Estados Unidos