Oligogenic approaches to the predisposition of asthma in ethnically diverse populations.

Abstract

Using the genome-wide screening data of the Collaborative Study on the Genetics of Asthma (CSGA) (226 families, 1,461 genotyped subjects, 323 marker loci) and Hutterite studies (129 families, 690 genotyped subjects, 365 marker loci), we applied a genetic similarity function in order to quantify the inter-individual genetic distances d(xi,xj) between feature vectors xi, xj made up by the allelic patterns of subjects i,j with respect to loci li, l2,..., ln. Based on this similarity function, we structurally decomposed the genetic diversity of the CSGA population in order to address the question of ethnicity-related asthma vulnerability for genetically homogenous CSGA subgroups. The question of ethnicity-independent asthma vulnerability was investigated with all CSGA families as training and the Hutterite families as replication samples. We evaluated the 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 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 18 vulnerability loci on chromosomes 1, 3, 4, 5, 6, 8, 12, 13, and 14, which were remarkably reproducible in the CSGA and the Hutterite data and constituted an ethnicity-independent oligogenic model.