title: Admixture-matched case-control study: a practical approach for genetic association studies in admixed populations.
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 FEV(1), 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, beta(2) adrenergic receptor (beta(2)AR) and DeltaFEF(25-75), 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.
authors.affiliation: Department of Medicine, Study of African American, Asthma, Genes and Environments, SAGE, University of California, 0833, San Francisco, 94143-0833, USA. hut1@itsa.ucsf.edu
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Tsai
authors.forename: Jennifer Y
authors.initials: JY
authors.lastname: Kho
authors.forename: Nishat
authors.initials: N
authors.lastname: Shaikh
authors.forename: Shweta
authors.initials: S
authors.lastname: Choudhry
authors.forename: Mariam
authors.initials: M
authors.lastname: Naqvi
authors.forename: Daniel
authors.initials: D
authors.lastname: Navarro
authors.forename: Henry
authors.initials: H
authors.lastname: Matallana
authors.forename: Richard
authors.initials: R
authors.lastname: Castro
authors.forename: Craig M
authors.initials: CM
authors.lastname: Lilly
authors.forename: H George
authors.initials: HG
authors.lastname: Watson
authors.forename: Kelley
authors.initials: K
authors.lastname: Meade
authors.forename: Michael
authors.initials: M
authors.lastname: Lenoir
authors.forename: Shannon
authors.initials: S
authors.lastname: Thyne
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.forename: Esteban González
authors.initials: EG
authors.lastname: Burchard
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D015986:Confounding Factors, Epidemiologic; D003710:Demography; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D001741:Black or African American
chemical_list: D018343:Receptors, Adrenergic, beta-2