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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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    1. Joscha Gretzinger & Duncan Sayer & Pierre Justeau & Eveline Altena & Maria Pala & Katharina Dulias & Ceiridwen J. Edwards & Susanne Jodoin & Laura Lacher & Susanna Sabin & Åshild J. Vågene & Wolfgang , 2022. "The Anglo-Saxon migration and the formation of the early English gene pool," Nature, Nature, vol. 610(7930), pages 112-119, October.
    2. John Novembre & Toby Johnson & Katarzyna Bryc & Zoltán Kutalik & Adam R. Boyko & Adam Auton & Amit Indap & Karen S. King & Sven Bergmann & Matthew R. Nelson & Matthew Stephens & Carlos D. Bustamante, 2008. "Genes mirror geography within Europe," Nature, Nature, vol. 456(7219), pages 274-274, November.
    3. Iosif Lazaridis & Nick Patterson & Alissa Mittnik & Gabriel Renaud & Swapan Mallick & Karola Kirsanow & Peter H. Sudmant & Joshua G. Schraiber & Sergi Castellano & Mark Lipson & Bonnie Berger & Christ, 2014. "Ancient human genomes suggest three ancestral populations for present-day Europeans," Nature, Nature, vol. 513(7518), pages 409-413, September.
    4. Rasika Ann Mathias & Margaret A. Taub & Christopher R. Gignoux & Wenqing Fu & Shaila Musharoff & Timothy D. O'Connor & Candelaria Vergara & Dara G. Torgerson & Maria Pino-Yanes & Suyash S. Shringarpur, 2016. "A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome," Nature Communications, Nature, vol. 7(1), pages 1-10, November.
    5. Daniel John Lawson & Garrett Hellenthal & Simon Myers & Daniel Falush, 2012. "Inference of Population Structure using Dense Haplotype Data," PLOS Genetics, Public Library of Science, vol. 8(1), pages 1-16, January.
    6. Charrad, Malika & Ghazzali, Nadia & Boiteau, Véronique & Niknafs, Azam, 2014. "NbClust: An R Package for Determining the Relevant Number of Clusters in a Data Set," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 61(i06).
    7. Daniel Taliun & Daniel N. Harris & Michael D. Kessler & Jedidiah Carlson & Zachary A. Szpiech & Raul Torres & Sarah A. Gagliano Taliun & André Corvelo & Stephanie M. Gogarten & Hyun Min Kang & Achille, 2021. "Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program," Nature, Nature, vol. 590(7845), pages 290-299, February.
    8. Adam E. Locke & Bratati Kahali & Sonja I. Berndt & Anne E. Justice & Tune H. Pers & Felix R. Day & Corey Powell & Sailaja Vedantam & Martin L. Buchkovich & Jian Yang & Damien C. Croteau-Chonka & Tonu , 2015. "Genetic studies of body mass index yield new insights for obesity biology," Nature, Nature, vol. 518(7538), pages 197-206, February.
    9. John Novembre & Toby Johnson & Katarzyna Bryc & Zoltán Kutalik & Adam R. Boyko & Adam Auton & Amit Indap & Karen S. King & Sven Bergmann & Matthew R. Nelson & Matthew Stephens & Carlos D. Bustamante, 2008. "Genes mirror geography within Europe," Nature, Nature, vol. 456(7218), pages 98-101, November.
    10. Andrés Moreno-Estrada & Simon Gravel & Fouad Zakharia & Jacob L McCauley & Jake K Byrnes & Christopher R Gignoux & Patricia A Ortiz-Tello & Ricardo J Martínez & Dale J Hedges & Richard W Morris & Cele, 2013. "Reconstructing the Population Genetic History of the Caribbean," PLOS Genetics, Public Library of Science, vol. 9(11), pages 1-19, November.
    11. Ashot Margaryan & Daniel J. Lawson & Martin Sikora & Fernando Racimo & Simon Rasmussen & Ida Moltke & Lara M. Cassidy & Emil Jørsboe & Andrés Ingason & Mikkel W. Pedersen & Thorfinn Korneliussen & Hel, 2020. "Population genomics of the Viking world," Nature, Nature, vol. 585(7825), pages 390-396, September.
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