Pathway analysis considers sets of genes in aggregate. Negative aggregate results could miss true over-representation of small p-values in a small number of hypothesis-driven candidate genes. Table 3a depicts the ISC findings for the 10 most-studied hypothesis-driven candidate genes. There was inadequate coverage for two small genes (DRD4 and APOE), and the remainder had good SNP densities but weak ISC results with none surviving a liberal gene-wise Bonferroni correction. Figure S2 depicts these genes and highlights regions of conspicuous attention in the literature (COMT/val58met, DRD3/ser9gly, DRD2/Taq1A, HTR2A/T102C, NRG1/HapICE, BDNF/val66met, DTNBP1, and SLC6A4/HTTLPR). The ISC results do not implicate common genetic variation in these genes. Although the region containing SLC6A4 shows no signal, the widely-studied promoter polymorphism (HTTLPR) was not directly genotyped and neighboring SNPs are in low linkage disequilibrium (Konneker et al., in press).
