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

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 chi2 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.