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

Area of Science:

• Population Genetics
• Genetic Epidemiology
• Statistical Genetics

Background:

• Genetic association studies in admixed populations face confounding from population stratification.
• The transmission/disequilibrium test (TDT) controls for stratification but is costly and impractical for late-onset diseases.

Purpose of the Study:

• To evaluate the efficacy of admixture-matched case-control designs in mitigating population stratification in genetic association studies.
• To assess the utility of this strategy in the Study of African American, Asthma, Genes and Environments cohort.

Main Methods:

• Recruited African American participants with matched admixture distributions between cases and controls.
• Performed association tests for asthma-related traits with ancestry.
• Examined genetic variants in the beta(2) adrenergic receptor (beta(2)AR) gene for association with asthma phenotypes.

Main Results:

• Admixture distributions were nearly identical in cases and controls.
• FEV(1) (forced expiratory volume in 1 second) was associated with ancestry (P=0.01) after adjusting for covariates.
• Population stratification did not confound genetic associations, as demonstrated by the beta(2)AR example.

Conclusions:

• Admixture-matched case-control designs are an efficient strategy to control for population stratification confounding.
• This approach offers a practical alternative for genetic association studies in admixed populations, particularly for complex and late-onset diseases.