Second, it is possible that the major hypotheses that drove the selection of many candidate genes are incorrect. SZGene candidate genes were selected for many different reasons and some resulted from genome-wide linkage screens (most notably NRG1 and DTNBP1) (Stefansson et al., 2002, Straub et al., 2002). However, the ISC GWAS results did not lend support for common variation contributing to schizophrenia - either for candidate genes from the literature as a whole, or for the specific pathways from which candidate genes were frequently selected. For the full set of hypothesis-driven candidate genes, there was nominally significant support for an over-representation of small ISC p-values. However, the effect was marginal, and the results were not significant when corrected for potential bias caused by linkage disequilibrium between genes. We found no support for an aggregate effect of hypothesis-driven candidate genes contributing to SCZ risk using a risk profile generated from the SNPs within these genes. This pattern of results is not consistent with robust or notable collective contribution of common variation within the hypothesis-driven candidate genes to schizophrenia based on the
