Investigating association of four gene regions (GABRB3, MAOB, PAH, and SLC6A4) with five symptoms in schizophrenia

Psychiatry Res. 2012 Jul 30;198(2):202-6. doi: 10.1016/j.psychres.2011.12.035. Epub 2012 Mar 12.

Abstract

Recently, microsatellite polymorphisms have been reported to be associated with four genes, GABRB3, MAOB, PAH, and SLC6A4, and their relationships have been tested to five symptom factors: hallucinations, delusions, negative symptoms, mania, and depression. These factors were frequently present in schizophrenia spectrum disorders in the Irish Study of High Density Schizophrenia Families (ISHDSF) with a proband with the diagnosis of schizophrenia (Bergen et al., 2009). Of these, GABRB3 and PAH were reported to be significantly associated with hallucinations and delusions in a 90-family subset of the ISHDSF, respectively. In this study, we tested the association of genetic markers from these four gene regions with the approximate five clinical symptoms, based upon 256 schizophrenia patients, with genotypic data obtained by higher resolution single nucleotide polymorphism (SNP) genotyping. We found one GABRB3 SNP (rs1426891, 70.8kb downstream of this gene) and haplotype constructed by three SNPs (rs1426891, rs2912602, and rs2912600) were significantly associated with hallucinations in Caucasians after Bonferroni correction for multiple testing (Bonferroni corrected P: 0.032 and 0.016, respectively). Additionally, we found one haplotype constructed by two SNPs, rs5905587-rs37615860, in MAOB/NDP gene region was significantly associated with delusions in all samples tested (Bonferroni corrected P: 0.048). These results provide additional evidence that GABRB3 and MAOB/NDP gene regions might constitute risk factors for hallucinations and delusions in schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Delusions / genetics
  • Female
  • Genetic Association Studies / methods
  • Genetic Association Studies / statistics & numerical data
  • Genetic Predisposition to Disease / genetics
  • Hallucinations / genetics
  • Haplotypes
  • Humans
  • Male
  • Monoamine Oxidase / genetics*
  • Phenylalanine Hydroxylase / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, GABA-A / genetics*
  • Schizophrenia / diagnosis
  • Schizophrenia / genetics*
  • Serotonin Plasma Membrane Transport Proteins / genetics*

Substances

  • GABRB3 protein, human
  • Receptors, GABA-A
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Phenylalanine Hydroxylase
  • Monoamine Oxidase