Gene-based tests can be a powerful alternative to tests of individual SNPs, especially when there are several causal SNPs in a gene. It is possible in such a circumstance that the p values might not be small enough to be distinguishable from noise. We conducted gene-based tests of 17,601 autosomal genes available in VEGAS (Liu et al., 2010). 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 SNPs with regulatory functions and SNPs in LD with those in the gene proper, VEGAS includes SNPs spanning a small region on each end of the gene. Because the p values were produced by RFGLS, they accurately reflect the clustered nature of our sample. A threshold of 2.84 × 10−6 was used for determining statistical significance, which corrects for the number of different genes.
