A novel relationship for schizophrenia, bipolar and major depressive disorder: a hint from chromosome 2 high density association screen

Abstract： Background ：Convergent evidence from genetics, symptology and psychopharmacology imply that there are some intrinsic connection betweem schizophrenia (SCZ) , bipolar disorder (BPD) and major depressive disorder (MDD). Also, any two or even three of these disorder could co-existe in some families. Methods： A total of 47,103 SNPs on chromosome 2 were genotyped by Affymetrix Genome-Wide Human SNP array 6.0 on 119 SCZ, 253 BPD (type-Ⅰ) , 177 MDD, and 1000 controls. Results：Associated loci were comprehensively revealed and outstanding susceptibility genes were identified including ACVR1, BCL11A, CNTNAP5, CRIM1, DNER, DTNB, ERBB4, FSHR, IKZF2, LRP1B, LRRTM4, LYPD6B, MYO3B, NOL10, NPAS2, NRXN1, PARD3B, PID1, PKP4, PLCL1, SPAG16, SPTBN1, THADA, TRPM8, UPP2 and ZNF385B. Unexpectedly, flanking genes for up to 98.3 % of associated SNPs were replicated ( P ≦9.9 x 10 -8 ) in an enlarged cohort of 986 SCZ cases. Conclusions ：Bipolar disorder and major depressive disorder are subtypes of schizophrenia.