We used VEGAS (Liu et al., 2010) to conduct gene-based tests of all 17,601 genes identified by VEGAS, to parallel our genome-wide scan of individual SNPs. VEGAS aggregates the effects of all SNPs within a gene by converting the p-values for each SNP into a chi-squared statistic and summing these into a single score, which is adjusted for LD between the SNPs (see Iacono et al., 2014). In order to capture regulatory SNPs and those in LD with SNPs in the gene proper, VEGAS includes all SNPs within 50 kilobases of each end of the gene. Because the p-values were produced by RFGLS, they accurately reflect the clustered nature of our sample. The null distribution of the test statistic in the presence of LD is determined using Monte Carlo methods and the LD structure of a reference sample from HapMap, for which purpose we used the CEU sample of Caucasians. A Bonferroni-corrected threshold of 2.84 × 10−6 was used to determine statistical significance.
