Common sequence variants in the major histocompatibility complex region associate with cerebral ventricular size in schizophrenia

Biol Psychiatry. 2011 Oct 1;70(7):696-8. doi: 10.1016/j.biopsych.2011.02.034. Epub 2011 Apr 22.

Abstract

Background: Because of evidence from genetic linkage and genome-wide association studies, as well as suggested involvement of infection, the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1 has been implicated in the development of schizophrenia.

Methods: Here, we investigated how gene variants across the MHC region are associated with brain structure in a large ethnically homogenous sample (n = 420), including patients with schizophrenia spectrum disorders and other severe mental illness and healthy control subjects.

Results: We demonstrate highly significant associations between common gene markers in the MHC region and cerebral ventricular volume specifically in schizophrenia spectrum patients (uncorrected p values between 1.16 × 10⁻⁴ and 2.00 × 10⁻⁷). One single nucleotide polymorphism, rs2596532, survives Bonferroni correction for multiple testing across all single nucleotide polymorphisms and brain structure measures (adjusted p value 5.59 × 10⁻⁴).

Conclusions: The results indicate that MHC variants are implicated in characteristic brain abnormalities of schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / pathology
  • Cerebral Ventricles / pathology*
  • Genetic Predisposition to Disease / genetics
  • Genetic Predisposition to Disease / psychology
  • Genotype
  • Magnetic Resonance Imaging
  • Major Histocompatibility Complex / genetics*
  • Neuroimaging / methods
  • Neuroimaging / statistics & numerical data
  • Polymorphism, Single Nucleotide / genetics
  • Schizophrenia / genetics*
  • Schizophrenia / pathology*