Genome-Wide Epistasis Screening for Asthma-Associated Traits

• Activity Number: 186
• Type: Invited
• Date/Time: Monday, August 1, 2011 : 10:30 AM to 12:20 PM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Elena S. Gusareva*+ and Jeroen S. Huyghe and Elena S. Gusareva
• Companies: University of Liège and University of Antwerp and University of Liège
• Keywords: eosinophil counts ; asthma genes ; genome-wide association study ; gene-gene interactions

Abstract

Genome-wide association (GWA) studies of asthma and associated traits have identified numerous genes. A substantial portion of the heritability of these traits remains unexplained. Some variants, not detectable via main effects GWA study may manifest themselves only in interaction with other variants. To search for interacting genes involved in regulation of asthma associated traits (total IgE, eosinophils, FEV1, FVC, FEV1/FVC) we performed GWA epistasis screening in two family groups of asthma patients:CAMP (Childhood Asthma Management Program:814 cases and 467 trios) and CARE (Childhood Asthma Research and Education:796 cases and 338 trios) [dbGaP accession number phs000166.v1.p1.c1]. Individuals were genotyped with the Aymetrix 6.0 array. After quality control 574922 and 575010 SNPs in CAMP and CARE respectively, were tested with FBAT. No main effects genome-wide significant associations were found. We prioritized candidate pairs of SNPs for MB-MDR epistasis screening using Biofilter leading to 7632 SNPs for CAMP and 7603 SNPs for CARE. The most significant pair-wise interaction was identified between SNPs from loci 7p21.1 and 12q23.3 influencing eosinophil level in asthmatics.