Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: The Genes-environments & Admixture in Latino Americans study

Abstract

Background Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations and replication of positive associations has been inconsistent. Objective To identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping. Methods Latino children with asthma (n = 1,893) and healthy controls (n = 1,881) were recruited from five sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci. Results We identified a significant association between ancestry and asthma at 6p21 (lowest p-value: rs2523924, p < 5 × 10−6). This association replicates in a meta-analysis of the EVE Asthma Consortium (p = 0.01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between the 17q21 asthma in Latinos (IKZF3, lowest p-value: rs90792, OR: 0.67, 95% CI 0.61 – 0.75, p = 6 × 10−13) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies. Conclusions Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, while genome-wide association confirms the previously identified locus on 17q21.

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

“…Extensive socioeconomic data were collected for each individual as a part of the Genes-Environments & Admixture in Latino Americans II (GALAII) study (17,18) (Materials and Methods and SI Appendix, Table S1). All of the offspring were genotyped, and the genomic ancestries of the offspring and each of their parents were computationally inferred.…”

“…In particular, our mathematical model illustrates how recessive risk alleles have inflated homozygosity in populations with strong assortative mating. An important agenda in epidemiology has been to understand the inflated prevalence of asthma and lung diseases such as Hermansky-Pudlak syndrome in Puerto Ricans (17,32). Our analysis suggests that assortative mating can be a significant factor, and it should be incorporated into epidemiological models of these diseases.…”

“…For each participant in the study, all four grandparents self-identified as Puerto Rican or Mexican. For each participant, genotypes were measured on the Affymetrix Axiom LAT1 array (>800,000 SNPs) designed for Latino populations, with quality control as previously described (17,18). The GALAII dataset also included information about the socioeconomic status of the participants and their parents, as described in detail in SI Appendix.…”

Air Pollution and Lung Function in Minority Youth with Asthma in the GALA II (Genes–Environments and Admixture in Latino Americans) and SAGE II (Study of African Americans, Asthma, Genes, and Environments) Studies

“…In addition, we have shown that genetic African ancestry is associated with increased risk of asthma in Latino children, whereas, conversely, Native American ancestry was associated with lower odds of asthma, and that African ancestry was associated with reduced lung function among children with asthma (23). Furthermore, alleles protective for the risk of asthma have been found to be more common in Native American populations, and, among Latinos, have been found in greater frequency among Mexican populations compared with other Latinos (23)(24)(25). Specific gene variants have also been linked to increased susceptibility of asthma in the presence of air pollution (26)(27)(28).…”

“…We evaluated genetic ancestry using methods described elsewhere (24). Briefly, we calculated the proportion of genetic ancestry by first genotyping all subjects with the Axiom LAT1 array (World Array 4; Affymetrix, Santa Clara, CA) (30).…”