Analysis of protocadherin alpha gene enhancer polymorphism in bipolar disorder and schizophrenia

Erika Pedrosa, Radu Stefanescu, Benjamin Margolis, Oriana Petruolo, Yungtai Lo, Karen Nolan, Tomas Novak, Pavla Stopkova, Herbert M. Lachman

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Cadherins and protocadherins are cell adhesion proteins that play an important role in neuronal migration, differentiation and synaptogenesis, properties that make them targets to consider in schizophrenia (SZ) and bipolar disorder (BD) pathogenesis. Consequently, allelic variation occurring in protocadherin and cadherin encoding genes that map to regions of the genome targeted in SZ and BD linkage studies are particularly strong candidates to consider. One such set of candidate genes is the 5q31-linked PCDH family, which consists of more than 50 exons encoding three related, though distinct family members - α, β, and γ - which can generate thousands of different protocadherin proteins through alternative promoter usage and cis-alternative splicing. In this study, we focused on a SNP, rs31745, which is located in a putative PCDHα enhancer mapped by ChIP-chip using antibodies to covalently modified histone H3. A striking increase in homozygotes for the minor allele at this locus was detected in patients with BD. Molecular analysis revealed that the SNP causes allele-specific changes in binding to a brain protein. The findings suggest that the 5q31-linked PCDH locus should be more thoroughly considered as a disease-susceptibility locus in psychiatric disorders.

Original languageEnglish (US)
Pages (from-to)210-219
Number of pages10
JournalSchizophrenia Research
Issue number1-3
StatePublished - Jul 2008


  • Bipolar disorder
  • Cadherin schizophrenia
  • Chromatin
  • Protocadherin

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


Dive into the research topics of 'Analysis of protocadherin alpha gene enhancer polymorphism in bipolar disorder and schizophrenia'. Together they form a unique fingerprint.

Cite this