Integrative genome-wide association analysis of cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders

Mol Psychiatry. 2011 Apr;16(4):452-61. doi: 10.1038/mp.2010.23. Epub 2010 Mar 23.


Cytoarchitectural abnormalities have been described in the prefrontal cortex (PFC) of subjects with psychiatric disorders. We explored the possible genetic causalities that may underlie the cytoarchitectural abnormalities of calbindin-containing γ-aminobutyric acid (GABA)ergic neurons and perineuronal oligodendrocytes in the PFC of subjects with psychiatric disorders by converging results from genome-wide single-nucleotide polymorphism (SNP) scans for the traits and expression SNP (eSNP) associations. In the initial genome-wide scans, we identified several development- and apoptosis-related genes associated with the cytoarchitectural traits. Moreover, the susceptibility gene for bipolar disorder, PPP2R2C, was found to be associated with the number of perineuronal oligodendrocytes. Further eSNP analyses indicated that two novel candidate genes, RAB2A and SLC38A1, were associated with the density of calbindin-positive neurons and the number of perineuronal oligodendrocytes, respectively. Our findings may provide novel insights into the genetic causalities associated with cytoarchitectural abnormalities in the PFC of subjects with major psychiatric disorders as well as into the etiology of such disorders.

MeSH terms

  • Adult
  • Amino Acid Transport System A / genetics*
  • Calbindins
  • Databases, Genetic
  • Female
  • Gene Expression Profiling
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Mental Disorders / genetics*
  • Mental Disorders / pathology*
  • Middle Aged
  • Oligodendroglia / pathology
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide / genetics*
  • Prefrontal Cortex / pathology*
  • Protein Phosphatase 2 / genetics
  • S100 Calcium Binding Protein G / genetics*
  • gamma-Aminobutyric Acid / genetics
  • rab2 GTP-Binding Protein / genetics


  • Amino Acid Transport System A
  • Calbindins
  • PPP2R2C protein, human
  • S100 Calcium Binding Protein G
  • SLC38A1 protein, human
  • gamma-Aminobutyric Acid
  • Protein Phosphatase 2
  • rab2 GTP-Binding Protein