We advise caution in interpreting the evidence for association of SNPs on 3p21.1 with a broad mood disorder phenotype based on the combined PGC MDD and BIP discovery samples (minimum P = 5.9×10−9 at rs2535629, chr3:52808259). Evidence to date suggests that this locus is associated with BIP66 and schizophrenia,36 and an even broader association was suggested by a PGC meta-analysis of MDD, BIP, schizophrenia, ADHD and autism. This separate PGC analysis included nearly all of the samples reported here, and the top finding was again for rs2535629 (P = 2.5×10−12).75 The BIP sample made the strongest contribution to the combined analysis (OR = 1.15) followed by schizophrenia (OR = 1.10), MDD (OR = 1.10), ADHD (OR = 1.05) and autism (OR = 1.05). Although a five-disorder model was statistically the most likely and significant heterogeneity of ORs across disorders was not detected, the MDD replication data reported here raise some questions whether MDD also has an association in this region. We obtained MDD replication data for two SNPs on 3p21.1 (Supplementary Table S18), and observed no additional support for association
