Analysis of four genes involved in the neurodevelopment shows association of rs4307059 polymorphism in the cadherin 9/10 region with completed suicide

Neuropsychobiology. 2012;66(2):134-40. doi: 10.1159/000339559. Epub 2012 Jul 27.

Abstract

Background: We hypothesized that DNA variants affecting neurodevelopment such as rs4307059 (CDH10/CDH9), rs930752 (NRXN1), rs6265 (BDNF) or rs10868235 (NTRK2) may predispose to completed suicide.

Methodology: We used a case-control two-stage approach based on a discovery cohort (557 cases and ∼550 controls) and replication cohort (159 cases and 186 controls). The suicides were ascertained as consecutive cases autopsied at the Department of Forensic Medicine, Medical University of Warsaw, Poland.

Results: In the discovery cohort we found an association between suicide and the CC genotype in the rs4307059 polymorphism (OR 1.64, p = 0.012). The trend for an overrepresentation of the CC homozygotes among suicides was replicated in the second cohort (OR 1.97, p = 0.056). Analysis in the pooled cohorts showed that rs4307059 CC was associated with completed suicide (OR 1.71, p = 0.002) also after Bonferroni correction (p(cor.) = 0.024). In an exploratory search for genotype-phenotype correlation we found that males with the rs4307059 CC genotype committed suicide earlier than those with CT/TT genotypes (p = 0.049).

Conclusions: The CC genotype of rs4307059 located in the region between CDH9 and CDH10 is associated with completed suicide in a Polish cohort.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Brain-Derived Neurotrophic Factor / genetics
  • Cadherins / genetics*
  • Calcium-Binding Proteins
  • Case-Control Studies
  • Cell Adhesion Molecules, Neuronal / genetics
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Mental Disorders / genetics*
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Neural Cell Adhesion Molecules
  • Poland
  • Polymorphism, Single Nucleotide
  • Receptor, trkB / genetics
  • Suicide*

Substances

  • Brain-Derived Neurotrophic Factor
  • CDH10 protein, human
  • CDH9 protein, human
  • Cadherins
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules, Neuronal
  • NRXN1 protein, human
  • Nerve Tissue Proteins
  • Neural Cell Adhesion Molecules
  • Receptor, trkB