Beyond our primary meta-analysis of single marker GWAS findings, we also conducted secondary analyses to determine whether any known biological pathways harbored an excess of SNPs with small p-values. Specifically, to interrogate the data for evidence of enriched association to known biological pathways we conducted pathway analysis using ConsensusPathDB (http://cpdb.molgen.mpg.de/), a human-centric meta-database of functional biological data, compiled from 30 separate public sources of biological interactions (Kamburov et al., 2011). All alcohol consumption-associated SNPs with meta-analysis p<0.01 were matched to the closest gene +25 kb using RefSeq (GRCh37) coordinate information. All implicated genes were assembled into a final non-redundant gene list, comprising 2590 (mean consumption) and 2506 (developmental trajectory) genes. For each of the 4601 reference pathways present in ConsensusPathDB, a hypergeometric test was performed to calculate the significance of the overlap between the genes from our putative susceptibility list and those present in each reference pathway. FDR was implemented to adjust significance for the large number of tests performed.
