In order to determine if there are genes which harbour an excess of associated variants, we conducted a gene-based test (VEGAS) that can be used for GWAS with related individuals (Liu, McRae, et al., 2010). Genes are functional groups of nucleotides that code for proteins. The test summarises evidence for association on a per gene basis by considering the p-value of all SNPs within genes (including +/−50kb from the 5′ and 3′ UTR), while accounting for linkage disequilibrium (LD) and number of SNPs per gene1. The gene-based test identifies genes which show more signal of association than expected by chance given their length and LD between the SNPs. As such it tests for a different genetic architecture of genes than single SNP tests. The relevance of the gene-based test depends on the underlying genetic architecture of genes which is unknown and which is expected to differ between genes. Because we perform eight gene-based association tests each including 17,206 autosomal genes, we consider genes with a p-value below α = 3.6*10−7 (0.05/(8*17,206)) to be significant.
