Genome-Wide Association Study in the Quebec Founder Population Generates Map of Interacting Genes Associated with Schizophrenia

Nouzha Paquin, John Realson, Pascal Croteau, Jonathan Segal, Micheline Lapalme, Bruno Paquin, Paul Van Eerdewegh, John Hooper, Abdelmajid Belouchi, Tim Keith
Genizon BioSiences, 880 McCaffrey, St. Laurent, Quebec, H4T 2C7, Canada

We have performed a genome-wide association study (GWAS) for schizophrenia, using samples from the Quebec Founder Population (QFP). The schizophrenia phenotype was determined according to the DSM-IV criteria. The controls were self-declared free of psychiatric disorders. A total of 516 cases and 516 controls were individually genotyped using the Illumina Infinium platform. The marker map consisted of Illumina's HAP300 chip (317,504 tag SNPs) augmented with 56,683 SNPs chosen to reflect the linkage disequilibrium (LD) structure of the QFP, based on a study of that structure in 1,000 individuals. Genome-wide haplotype case-control association analysis was carried out using proprietary software. The haplotype testing algorithms are described together with methods for and results of genome-wide significance testing using a permutation-based approach. Nineteen loci met the criteria for genome-wide significance and examples of these are described, including information on the length of the regions and the relevance of the encoded genes in relation to the disease. Additional regions were identified from gender-specific and paranoid sub-phenotype analyses and the characteristics of these are described. Examples include regions for which the -Log10 P values significantly increased in comparison to the full sample set. The candidate regions are genetically well resolved with many of them containing only 1 or 2 genes. A GeneMap consisting of networks of interacting disease genes and their biochemical pathways, derived from the results of the genome wide association study, will be outlined, together with the nature of the pathways, including many that appear to be relevant to the disease and others that point to novel pathways.