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Genetic vulnerability to atopy and asthma in ethnically diverse populations: analysis of a multinational sample

Item Type:Article
Title:Genetic vulnerability to atopy and asthma in ethnically diverse populations: analysis of a multinational sample
Creators Name:Scharfetter, C., Kurz, T., Hoffmann, K., Deichmann, K.A. and Stassen, H.H.
Abstract:Using mite sensitization as endophenotype of atopy and asthma and family data from three European ethnicities (44 German, 26 Portuguese, and 19 British families with a total of 410 subjects) we searched for an oligogenic configuration of susceptibility loci that was equally valid for all three ethnicity-related samples. Our novel multilocus genotype-to-phenotype search strategy was based on a genetic similarity function that allowed us to quantify the inter-individual genetic distances d(xi, xj) between feature vectors xi, xj made up of the allelic genotype patterns of any two subjects i, j with respect to n loci l1, l 2, .. ln. Thus, we were able to quantify the between-population, the within-population, and the within-family genetic similarities. The question of ethnicity-independent susceptibility was addressed by treating the German families - ascertained from a population with intermediate prevalences of atopy and asthma - as "training" samples, while the British families - ascertained from a population with high prevalences of atopy and asthma - served as independent "test" samples, along with the Portuguese families who stemmed from a region with low prevalences of atopy and asthma. Relying upon the linkage paradigm, we evaluated the multilocus between-sib similarities which were expected to deviate from "0.5" in affected sib pairs if the region of interest contained markers close to disease-causing or protective genes. The reference value "0.5" was derived by determining the parent-offspring similarities which are always 0.5, irrespective of the affection status of parents and offspring. We found 11 vulnerability loci and 1 protective locus on chromosomes 2, 5, 6, 7, 8, 11, 12, 13, 15 and 19. These loci were reproducible across the ethnicities under comparison and constituted our ethnicity-independent oligogenic model of atopy and asthma susceptibility. Our results have cleared the way for systematic investigations into complex disorders, in particular psychiatric disorders, and to address the question of the extent to which genetic risk factors and their interactions constitute multigenic inheritance across populations and might constitute universal targets for treatment.
Keywords:Atopy, Asthma, Risk, Mite Sensitization, Genetic Diversity, Population Admixture
Source:Neurology Psychiatry and Brain Research
Publisher:Universitätsverlag Ulm
Page Range:27-36

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