Population stratification confounds genetic association studies among Latinos

Abstract

In the United States, asthma prevalence and mortality are the highest among Puerto Ricans and the lowest among Mexicans. Case-control association studies are a powerful strategy for identifying genes of modest effect in complex diseases. However, studies of complex disorders in admixed populations such as Latinos may be confounded by population stratification. We used ancestry informative markers (AIMs) to identify and correct for population stratification among Mexican and Puerto Rican subjects participating in case-control studies of asthma. Three hundred and sixty-two subjects with asthma (Mexican: 181, Puerto Rican: 181) and 359 ethnically matched controls (Mexican: 181, Puerto Rican: 178) were genotyped for 44 AIMs. We observed a greater than expected degree of association between pairs of AIMs on different chromosomes in Mexicans (P < 0.00001) and Puerto Ricans (P < 0.00002) providing evidence for population substructure and/or recent admixture. To assess the effect of population stratification on association studies of asthma, we measured differences in genetic background of cases and controls by comparing allele frequencies of the 44 AIMs. Among Puerto Ricans but not in Mexicans, we observed a significant overall difference in allele frequencies between cases and controls (P = 0.0002); of 44 AIMs tested, 8 (18%) were significantly associated with asthma. However, after adjustment for individual ancestry, only two of these markers remained significantly associated with the disease. Our findings suggest that empirical assessment of the effects of stratification is critical to appropriately interpret the results of case-control studies in admixed populations.

Genome-wide screen for asthma in Puerto Ricans: evidence for association with 5q23 region

“…We have previously shown that there is evidence of substantial confounding from population stratification in association studies of asthma in Latino populations (Choudhry et al 2006). Here, we confirm our previous findings using a much larger set of AIMs (n = 2730) suggesting that any association study of asthma in Latino populations should be tested and corrected for population stratification.…”

“…Although there are many potential explanations for this observation, including environmental and socioeconomic factors, one likely explanation is that the genetic predisposition to asthma differs among subgroups within the Latino population. Latinos are admixed and share varying proportions of West African, Native American and European ancestry (Choudhry et al 2006;Hanis et al 1991). The mixed ancestry of Latinos provides unique opportunities in epidemiological and genetic studies and may be useful in untangling complex gene-gene and gene-environment interactions in disease susceptibility Choudhry et al 2007).…”

Risk Factors for Proteinuria in HIV-Infected and -Uninfected Hispanic Drug Users

“…The study participants were mostly of Puerto Rican origin, who are a mix of European (predominant), Amerindian, and African American race. 15 The inclusion criteria for the parent study were: self-identified Hispanic ethnicity; age over 18 years; Spanish fluency; HIV seropositive and/or current drug use. Exclusion criteria were: pregnancy at recruitment; non-HIV associated malignancies; refusal to sign a consent form to release medical records; and chronic renal replacement therapy.…”

Relationship between hypertension and admixture in post-menopausal African American and Hispanic American women

“…14,[18][19][20] Although one prominent study concluded that Puerto Rican Americans are similar to Mexican Americans with a lower frequency of hypertension compared with non-Hispanic EUR Americans 21 this interpretation has been questioned based on methodological issues 22 and one cross-sectional study found a 2.6-fold risk for systolic hypertension in Puerto Rican Americans compared with non-Hispanic EUR Americans. 23 In addition, the differences in admixture among these populations may explain why some 2 but not other studies 16,17 have suggested that HA have lower frequency of hypertension than non-Hispanic EUR American populations.…”