Finally, we assessed the effect of individual GABA system genes using a gene-based test (VEGAS; Liu et al., 2010), which combines the test statistics from single-SNP analyses of all markers within a particular gene, then compares the resulting gene-based test statistic to a large number of simulated chi-square distributed gene-based test statistics, which are produced taking into account Hapmap (CEU) LD structure and gene length, and which approximate the observed gene-based test statistic under the null hypothesis. The p-value resulting from this gene-based test is thus the proportion of simulated test statistics that exceed the observed test statistic. This form of analysis can reveal whether there are disproportionately many markers with low p-values in a given gene. We also performed a variation on the gene-based test (the “Top-SNP” method) which compares the top-ranked marker in each gene to the simulated maximum element (itself the test statistic of a chi-squared 1 df variable) of the gene-based test statistic.
