We used VEGAS2 (Versatile Gene-based Association Study) [25], an updated version of VEGAS [26], to calculate gene-based p-values from the association results. This online software tool uses population-based estimates for linkage disequilibrium (LD) and SNP-based p-values from GWAS, to identify significant deviations from expected p-value distributions within genes, under the null. In VEGAS2, this information is derived using the 1000 Genomes phase 1 data, enabling improvements in the LD estimates and allows analysis of X-chromosome. The analysis provides a statistic for gene-based results that is sensitive to gene length and recombination hotspots, as well as identifying genes in which there are multiple independent signals across cases, each of which individually may not reach genome-wide significance. For our analysis we used the Asian reference data, selecting the Chinese reference panel to estimate LD within genes and calculate gene-based empirical tests of association. Margins of +/- 50kb were set for LD estimates and all chromosomes were included except chromosome Y and mitochondrial genes.
