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Unappreciated subcontinental admixture in Europeans and European Americans and implications for genetic epidemiology studies

Author

Listed:
  • Mateus H. Gouveia

    (National Institutes of Health)

  • Amy R. Bentley

    (National Institutes of Health)

  • Thiago P. Leal

    (Cleveland Clinic)

  • Eduardo Tarazona-Santos

    (Universidade Federal de Minas Gerais)

  • Carlos D. Bustamante

    (Stanford University)

  • Adebowale A. Adeyemo

    (National Institutes of Health)

  • Charles N. Rotimi

    (National Institutes of Health)

  • Daniel Shriner

    (National Institutes of Health)

Abstract

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.

Suggested Citation

  • Mateus H. Gouveia & Amy R. Bentley & Thiago P. Leal & Eduardo Tarazona-Santos & Carlos D. Bustamante & Adebowale A. Adeyemo & Charles N. Rotimi & Daniel Shriner, 2023. "Unappreciated subcontinental admixture in Europeans and European Americans and implications for genetic epidemiology studies," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42491-0
    DOI: 10.1038/s41467-023-42491-0
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