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 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 (SAGE). 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 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 (AIMs) 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, β 2 adrenergic receptor (β 2 AR) and ΔFEF 25-75 , an asthma-related phenotype, as an † Correspondence and reprint requests should be addressed to:

A review of psychiatric genetics research in the Brazilian population

“…It is argued that admixture-matched case-control strategies can efficiently control population stratification, 82 particularly collecting as much information about ethnicity as possible, in order to provide an accurate ethnic stratification and reduce false-positive results. However, this view is not consensual 83 and, particularly in Brazil, it has been demonstrated that physical appearance or self-reported background are not efficient predictors of genomic ancestrality.…”

Ethnicity-specific Gene–Gene Interaction between IL-13 and IL-4Rα among African Americans with Asthma

“…Recruitment and patient characteristics are described elsewhere and in detail in the online supplement (19). Briefly, as part of the Study of African Americans, Asthma, Genes, and Environments (SAGE), investigators recruited cases and control subjects from community clinics within San Francisco and Oakland, California.…”

Relationship between Ancestry Inferred By Molecular Analysis, Self-Report and Hetero-Classification

“…One of the problems of conducting association studies in miscegenated populations by using only self-reported ancestry or skin color as equivalents of ethnicity is the possibility of a spurious association with false-positive or false-negative results [23][24][25][26][27][28][29].…”

“…In most of the studies, single nucleotide polymorphisms (SNPs) were used [30][31][32][33], but insertion/deletion markers (INDELs) with small DNA fragments [29,34] and Short Tandem Repeats (STRs) [35] have also been employed.…”