A susceptibility locus for asthma-related traits on chromosome 7 revealed by genome-wide scan in a founder population

The genetics of asthma and atopy have been difficult to determine because t hese diseases are genetically heterogeneous and modified by environment. Th e pedigrees in our study (n=86) originate in eastern central Finland (Kainu u province). According to census records, this region had only 200 househol ds (2,000 inhabitants) in the mid sixteenth to mid seventeenth centuries. T he current population of 100.000 represents the expansion of these founders within the past 400 years. Because this population is relatively homogeneo us(1,2), we hypothesized that the molecular genetic mechanisms underlying a sthma might also have reduced heterogeneity and therefore be easier to diss ect than in mixed populations. A recent twin family study supported a stron g genetic component for asthma in Finland(3). We carried out a genome-wide scan for susceptibility loci in asthma in the Kainuu subpopulation. We iden tified two regions of suggestive linkage and studied them further with high er-density mapping. We obtained evidence for linkage in a 20-cM region of c hromosome 7p14-p15 for three phenotypes: asthma, a high level of immunoglob ulin E (IgE; atopy) and the combination of the phenotypes. The strongest li nkage was seen for high serum IgE(non-parametric linkage (NPL) score 3.9, P =0.0001), exceeding the threshold for genome-wide significance based on sim ulations. We also observed linkage between this locus and asthma or atopy i n two independent data sets.