test P = 0.042). Second, in the combined analysis of these 819 SNPs, 15 exceeded genome-wide significance (P<5×10−8) and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083–53 822 102, minimum P=5.9×10−9 at rs2535629; Supplementary Table S19, Supplementary Figure S20). The 116 SNPs in this region were all selected from the BIP sample (P < 0.0001), and none from the MDD sample. The region of strongest signal contained 84 SNPs from rs2878628 to rs2535629 (chr3:52 559 755–52 808 259). This region contains multiple genes: PBRM1 (chromatin remodeling and renal cell cancer), GNL3 (stem cell maintenance and tumorgenesis), GLT8D1, SPCS1, NEK4, the ITIH1-ITIH3-ITIH4 gene cluster (possibly involved in cancer), four micro-RNA and three small nucleolar RNA genes. This region had genome-wide significant findings in three prior GWAS: rs1042779 (chr3:52 796 051) for BIP,66 rs736408 (chr3:52 810 394) for a combined BIP-schizophrenia phenotype36 and rs2251219 (chr3:52 559 827) for a combined MDD-BIP phenotype67 (although a reanalysis suggested most of the signal arose from the BIP group).68 The PGC analyses include nearly all subjects in the prior reports, and thus cannot be considered independent evidence. As discussed below, we advise caution in interpreting this result.
