As an attempt to minimize false positives in our gene set enrichment analysis, we divided the Stage 1 GWAS cohorts with full genome-wide data into two sets of roughly equal size. We then used i-GSEA4GWAS (http://gsea4gwas.psych.ac.cn/)78 for each of the two GWAS data sets to assess enrichment of COPD GWAS loci in BioCarta (http://cgap.nci.nih.gov/Pathways/BioCarta_Pathways) and KEGG79 pathways as well as gene ontology (GO) terms80,81. We first evaluated GO terms and pathways with a false-discovery rate (FDR) less than 5% in both analysis sets and then used a more stringent threshold of FDR < 1% to evaluate overlap of GO term and pathway enrichment in our two analysis sets.
