A genome scan of asthma phenotypes in a large collection of families from Europe Australia and US

Abstract Rationale The prevalence of asthma and other allergic diseases has risen to above 10% over the past 2 decades. Genome wide screens for asthma phenotypes have been completed in several populations. Overall results from these genome scans differ significantly, which could mainly be attributed to the sample size, and the choice of phenotypes/populations. We conducted a genome scan using a large population to identify asthma susceptibility genes. Methods An asthma Genetics program was initiated at GSK in 1998 which includes the Genetics of Asthma International network (GAIN) and two independent collections from Denmark and Minnesota. We collected ∼1500 families from 13 collection centers in Europe Australia and US. A genome scan using 735 families was performed with 390 markers representing an approximate 7-cM genome scan set (752 affected sib pairs for Physician's Diagnosis of Asthma, PDA). Multi-point linkage analysis was performed with Genehunter using four phenotypes; PDA, atopic asthma, BHR (bronchial hyper-responsiveness) and strict asthma (2 of 3 symptoms + BHR). Results Preliminary results showed the following 5 chromosomal regions with a LOD greater than 2.0, Chromosome 1, LOD score 2.014 for atopic asthma; Chromosome 2, LOD score 2.23 for strict asthma and/ BHR; chromosome 4, LOD score 2.43 for BHR; chromosome 6, LOD score 2.06 for strict asthma; and chromosome 12, LOD score 2.03 for physician's diagnosis of asthma. Conclusions The improved power associated with the better sample size has led to the identification of several genomic regions linked to asthma, including a potentially novel locus on chromosome 4.