Human Genetics

, Volume 118, Issue 5, pp 626–639

Admixture-matched case-control study: a practical approach for genetic association studies in admixed populations

  • Hui-Ju Tsai
  • Jennifer Y. Kho
  • Nishat Shaikh
  • Shweta Choudhry
  • Mariam Naqvi
  • Daniel Navarro
  • Henry Matallana
  • Richard Castro
  • Craig M. Lilly
  • H. George Watson
  • Kelley Meade
  • Michael LeNoir
  • Shannon Thyne
  • Elad Ziv
  • Esteban González Burchard
Original Investigation

Abstract

Case-control genetic association studies in admixed populations are known to be susceptible to genetic confounding due to population stratification. The transmission/disequilibrium test (TDT) approach can avoid this problem. However, the TDT is expensive and impractical for late-onset diseases. Case-control study designs, in which, cases and controls are matched by admixture, can be an appealing and a suitable alternative for genetic association studies in admixed populations. In this study, we applied this matching strategy when recruiting our African American participants in the Study of African American, Asthma, Genes and Environments. Group admixture in this cohort consists of 83% African ancestry and 17% European ancestry, which was consistent with reports from other studies. By carrying out several complementary analyses, our results show that there is a substructure in the cohort, but that the admixture distributions are almost identical in cases and controls, and also in cases only. We performed association tests for asthma-related traits with ancestry, and only found that FEV1, a measure for baseline pulmonary function, was associated with ancestry after adjusting for socio-economic and environmental risk factors (P=0.01). We did not observe an excess of type I error rate in our association tests for ancestry informative markers and asthma-related phenotypes when ancestry was not adjusted in the analyses. Furthermore, using the association tests between genetic variants in a known asthma candidate gene, β2 adrenergic receptor (β2AR) and ΔFEF25–75, an asthma-related phenotype, as an example, we demonstrated population stratification was not a confounder in our genetic association. Our present work demonstrates that admixture-matched case-control strategies can efficiently control population stratification confounding in admixed populations.

Supplementary material

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Hui-Ju Tsai
    • 1
    • 2
  • Jennifer Y. Kho
    • 1
    • 2
  • Nishat Shaikh
    • 1
    • 2
  • Shweta Choudhry
    • 1
    • 2
  • Mariam Naqvi
    • 1
    • 2
  • Daniel Navarro
    • 1
    • 2
  • Henry Matallana
    • 1
    • 2
  • Richard Castro
    • 1
    • 2
  • Craig M. Lilly
    • 4
  • H. George Watson
    • 5
  • Kelley Meade
    • 6
  • Michael LeNoir
    • 7
  • Shannon Thyne
    • 1
  • Elad Ziv
    • 1
    • 3
  • Esteban González Burchard
    • 1
    • 2
    • 3
  1. 1.Department of Medicine, Study of African American, Asthma, Genes and Environments (SAGE)University of CaliforniaSan FranciscoUSA
  2. 2.Lung Biology Center, Study of African American, Asthma, Genes and Environments (SAGE)San Francisco General HospitalSan FranciscoUSA
  3. 3.Center for Human Genetics, Study of African American, Asthma, Genes and Environments (SAGE)University of CaliforniaSan FranciscoUSA
  4. 4.Brigham and Women’s HospitalBostonUSA
  5. 5.The James A. Watson Wellness CenterOaklandUSA
  6. 6.Children’s Hospital and Research InstituteOaklandUSA
  7. 7.Bay Area PediatricsOaklandUSA

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