Case-control admixture mapping in Latino populations enriches for known asthma-associated genes

Abstract

Background Polymorphisms in more than 100 genes have been associated with asthma susceptibility, yet much of the heritability remains to be explained. Asthma disproportionately affects different racial and ethnic groups in the United States, suggesting that admixture mapping is a useful strategy to identify novel asthma-associated loci. Objective We sought to identify novel asthma-associated loci in Latino populations using case-control admixture mapping. Methods We performed genome-wide admixture mapping by comparing levels of local Native American, European, and African ancestry between children with asthma and nonasthmatic control subjects in Puerto Rican and Mexican populations. Within candidate peaks, we performed allelic tests of association, controlling for differences in local ancestry. Results Between the 2 populations, we identified a total of 62 admixture mapping peaks at a P value of less than 10−3 that were significantly enriched for previously identified asthma-associated genes (P = .0051). One of the peaks was statistically significant based on 100 permutations in the Mexican sample (6q15); however, it was not significant in Puerto Rican subjects. Another peak was identified at nominal significance in both populations (8q12); however, the association was observed with different ancestries. Conclusion Case-control admixture mapping is a promising strategy for identifying novel asthma-associated loci in Latino populations and implicates genetic variation at 6q15 and 8q12 regions with asthma susceptibility. This approach might be useful for identifying regions that contribute to both shared and population-specific differences in asthma susceptibility.

Genetic and socioeconomic study of mate choice in Latinos reveals novel assortment patterns

“…All of the offspring were genotyped, and the genomic ancestries of the offspring and each of their parents were computationally inferred. To validate our findings, we also analyzed 231 Mexican trios and 258 Puerto Rican trios from the Genetics of Asthma in Latino Americans I (GALAI) study (19,20), where each member of the trio was genotyped.…”

Dysregulated invertebrate tropomyosin–dectin-1 interaction confers susceptibility to allergic diseases

“…For African Americans, we assumed a two-population model of admixture (European and African ancestry), and for Latinos, we assumed a three-population model (European, Native American, and African ancestry). Reference haplotypes were from the HapMap phase II CEU (European) and YRI (African), and 71 Native American individuals were genotyped on the Axiom LAT1 array as described previously (77). The association of each SNP with FEV 1 was performed using linear regression in PLINK 1.9 (78, 79).…”

Asthma Research for All of the United States

“…Admixture mapping provides an alternative approach to the typical GWAS model, allowing for greater power and discovery in admixed populations. 19,21 Health disparities in asthma are currently being ignored by the genetic community, but by expanding our research to include more diverse communities, we will be able to obtain a better understanding of the complexities of asthma for all of the United States and address the health disparities.…”

“…21 The study included 253 Puerto Rican and 276 Mexican subjects with asthma and their parents who were recruited from hospitals in the San Francisco Bay Area, New York City, Puerto Rico, and Mexico for the Genetics of Asthma in Latino Americans (GALA) study. Although this population size is considered underpowered for a traditional GWAS, Torgerson et al found that ancestry at the 8q12 locus was significantly associated with asthma in both Puerto Rican and Mexicans, but with Native American and African ancestry, respectively.…”