Genome-wide search for asthma susceptibility loci in a founder population. The Collaborative Study on the Genetics of Asthma

TLDR

Founder populations provide a powerful setting for mapping complex genetic traits due to their genetic homogeneity and reduced heterogeneity. The study aimed to discover genes influencing asthma and related phenotypes by conducting a genome‑wide screen in the Hutterite isolate. Researchers performed a genome‑wide scan of 361 primary and 292 replication Hutterite individuals using 292 autosomal and 3 X‑Y pseudoautosomal markers, applying semi‑parametric likelihood ratio χ² and transmission‑disequilibrium tests to detect linkage to asthma phenotypes. They identified 12 markers in 10 regions linked to asthma, with four regions replicating in both samples and a novel linkage at 3p24.2–22, suggesting that multiple common polymorphisms contribute to asthma susceptibility even in a founder population.

Abstract

Founder populations offer many advantages for mapping genetic traits, particularly complex traits that are likely to be genetically heterogeneous. To identify genes that influence asthma and asthma-associated phenotypes, we conducted a genome-wide screen in the Hutterites, a religious isolate of European ancestry. A primary sample of 361 individuals and a replication sample of 292 individuals were evaluated for asthma phenotypes according to a standardized protocol. A genome-wide screen has been completed using 292 autosomal and three X-Y pseudoautosomal markers. Using the semi-parametric likelihood ratio χ2 test and the transmission-disequilibrium test, we identified 12 markers in 10 regions that showed possible linkage to asthma or an associated phenotype (likelihood ratio P < 0.01). Markers in four regions (5q23–31, 12q15–24.1, 19q13 and 21q21) showed possible linkage in both the primary and replication samples and have also shown linkage to asthma phenotypes in other samples; two adjacent markers in one additional region (3p24.2–22) showing possible linkage is reported for the first time in the Hutterites. The results suggest that even in founder populations with a relatively small number of independent genomes, susceptibility alleles at many loci may influence asthma phenotypes and that these susceptibility alleles are likely to be common polymorphisms in the population.