A novel relationship for schizophrenia, bipolar and major depressive disorder Part 5: a hint from chromosome 5 high density association screen.

Familial clustering of schizophrenia (SCZ), bipolar disorder (BPD), and major depressive disorder (MDD) was systematically reported (Aukes, M. F. Genet Med 2012, 14, 338-341) and any two or even three of these disorders could co-exist in some families. In addition, evidence from symptomatology and psychopharmacology also imply that there are intrinsic connections between these three major disorders. A total of 56,569 single nucleotide polymorphism (SNPs) on chromosome 5 were genotyped by Affymetrix Genome-Wide Human SNP array 6.0 on 119 SCZ, 253 BPD (type-I), 177 MDD patients and 1000 controls. Associated SNPs and flanking genes was screen out systematically, and cadherin pathway genes (CDH6, CDH9, CDH10, CDH12, and CDH18) belong to outstanding genes. Unexpectedly, nearly all flanking genes of the associated SNPs distinctive for BPD and MDD were replicated in an enlarged cohort of 986 SCZ patients (P ≤ 9.9E-8). Considering multiple bits of evidence, our chromosome 5 analyses implicated that bipolar and major depressive disorder might be subtypes of schizophrenia rather than two independent disease entities. Also, cadherin pathway genes play important roles in the pathogenesis of the three major mental disorders.