Obvious disadvantages to a gene-wide approach are that we do not know the boundaries of genes, that the presence of linkage disequilibrium (LD) means that association to a physical location may not point to the particular co-terminous functional element, and many important signals will be contained within functional elements that do not correspond to genes. Nevertheless, it seems a reasonable first assumption that SNPs assigned to known functional elements (genes) would have a higher probability of being associated with disease than the remaining SNPs, even though some of the latter will span unknown functional elements. In order to test this, we counted the total number of SNPs designated by us as within genes surpassing nominal thresholds of p≤0.05, p≤0.01, and p≤0.001 in the observed dataset and also the total number of those not designated by us as within genes. We then compared the observed numbers with the null distributions for each as determined from the permutation datasets.
