We used the association results from the discovery + SAGE meta-analysis (i.e. Phase 1 ± Phase 2) for each of the primary traits (except CIP) to conduct a pathway analysis with the Ingenuity Pathway Analysis (IPA) software suite (http://www.ingenuity.com). First, the number of independent SNP association tests for each gene in the genome (only including SNPs within the transcribed portion of each gene) was computed according to the method of Li and Ji.26 We multiplied the smallest P-value within a gene by the number of independent SNPs in that gene and created a list of genes containing a SNP with gene-based multiple-test-corrected significance (Padj<0.05). The genes in the list were evaluated by pathway analysis to identify an overrepresentation of genes within defined canonical pathways based on information culled from multiple sources. A Fisher’s exact P-value was computed for each pathway indicating whether, after accounting for the total number of pathways and the number of genes in a given pathway, there were more significantly associated SNPs than would be expected by chance. Separate gene lists were created for the Sympcountadj and case-control results within each population.
