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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.

SUBMITTER: Tsai HJ

PROVIDER: S-EPMC3478103 | biostudies-literature | 2006 Jan

REPOSITORIES: biostudies-literature

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

Tsai Hui-Ju HJ Kho Jennifer Y JY Shaikh Nishat N Choudhry Shweta S Naqvi Mariam M Navarro Daniel D Matallana Henry H Castro Richard R Lilly Craig M CM Watson H George HG Meade Kelley K Lenoir Michael M Thyne Shannon S Ziv Elad E Burchard Esteban González EG

Human genetics 20051105 5

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 ...[more]

PMID: 16273390

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Project description:BackgroundThe prevalence and incidence of dementia are low in Nigeria, but high among African-Americans. In these populations there is a high frequency of the risk-conferring APOE-e4 allele, but the risk ratio is less than in Europeans. In an admixed population of older Cubans we explored the effects of ethnic identity and genetic admixture on APOE genotype, its association with dementia, and dementia prevalence.MethodsA cross-sectional catchment area survey of 2928 residents aged 65 and over, with a nested case-control study of individual admixture. Dementia diagnosis was established using 10/66 Dementia and DSM-IV criteria. APOE genotype was determined in 2520 participants, and genetic admixture in 235 dementia cases and 349 controls.ResultsMean African admixture proportions were 5.8% for 'white', 28.6% for 'mixed' and 49.6% for 'black' ethnic identities. All three groups were substantially admixed with considerable overlap. African admixture was linearly related to number of APOE-e4 alleles. One or more APOE-e4 alleles was associated with dementia in 'white' and 'black' but not 'mixed' groups but neither this, nor the interaction between APOE-e4 and African admixture (PR 0.52, 95% CI 0.13-2.08) were statistically significant. Neither ethnic identity nor African admixture was associated with dementia prevalence when assessed separately. However, considering their joint effects African versus European admixture was independently associated with a higher prevalence, and 'mixed' or 'black' identity with a lower prevalence of dementia.ConclusionsAPOE genotype is strongly associated with ancestry. Larger studies are needed to confirm whether the concentration of the high-risk allele in those with African ancestry is offset by an attenuation of its effect. Counter to our hypothesis, African admixture may be associated with higher risk of dementia. Although strongly correlated, effects of admixture and ethnic identity should be distinguished when assessing genetic and environmental contributions to disease risk in mixed ancestry populations.

Dataset Information

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

Publications

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

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