Using MAGMA, we undertook a primary analysis of 134 central nervous system (CNS)-related gene sets we have previously shown capture the excess copy number variation (CNV) burden in schizophrenia30. In a GWAS context, we now show that, collectively, this group of gene sets captures a disproportionately high fraction of h2SNP (30% of total heritability, enrichment = 1.63, P = 8.57 × 10−13, 46% of genic heritability; Supplementary Table 7). Of the 134 sets, 54 were nominally significant, of which 12 survived multiple-testing correction (family-wise error rate (FWER) P < 0.05; Supplementary Table 9), with no notable association for gene sets such as the ARC protein complex and the NMDAR protein network, that we have previously implicated in rare variant studies30,31. Stepwise conditional analysis, adjusting sequentially for the more strongly associated gene sets, resulted in six gene sets that were independently associated with schizophrenia (Table 2 and Supplementary Data). These extended from low-level molecular and subcellular processes to broad behavioral phenotypes. The most strongly associated gene set constituted the targets of the fragile X mental retardation protein (FMRP)32. FMRP is a
