Influence of ZNF804a on brain structure volumes and symptom severity in individuals with schizophrenia

Arch Gen Psychiatry. 2012 Sep;69(9):885-92. doi: 10.1001/archgenpsychiatry.2011.2116.


CONTEXT The single-nucleotide polymorphism rs1344706 in the gene ZNF804a has been associated with schizophrenia and with quantitative phenotypic features, including brain structure volume and the core symptoms of schizophrenia. OBJECTIVE To evaluate associations of rs1344706 with brain structure and the core symptoms of schizophrenia. DESIGN Case-control analysis of covariance. SETTING University-based research hospital. PARTICIPANTS Volunteer sample of 335 individuals with schizophrenia spectrum disorders (306 with core schizophrenia) and 198 healthy volunteers. MAIN OUTCOME MEASURES Cerebral cortical gray matter and white matter (WM) volumes (total and frontal, parietal, temporal, and occipital lobes), lateral ventricular cerebrospinal fluid volume, and symptom severity from the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms divided into 3 domains: psychotic, negative, and disorganized. RESULTS The rs1344706 genotype produced significant main effects on total, frontal, and parietal lobe WM volumes (F = 3.98, P = .02; F = 4.95, P = .007; and F = 3.08, P = .05, respectively). In the schizophrenia group, rs1344706 produced significant simple effects on total (F = 3.93, P = .02) and frontal WM volumes (F = 7.16, P < .001) and on psychotic symptom severity (F = 6.07, P = .003); the pattern of effects was concordant with risk allele carriers having larger volumes and more severe symptoms of disease than nonrisk homozygotes. In the healthy volunteer group, risk allele homozygotes had increased total WM volume compared with nonrisk allele carriers (F = 4.61, P = .03), replicating a previously reported association. CONCLUSIONS A growing body of evidence suggests that the risk allele of rs1347706 is associated with a distinctive set of phenotypic features in healthy volunteers and individuals with schizophrenia. Our study supports this assertion by finding that specific genotypes of the polymorphism are associated with brain structure volumes in individuals with schizophrenia and healthy volunteers and with symptom severity in schizophrenia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alleles*
  • Case-Control Studies
  • Cerebral Cortex / pathology
  • Female
  • Gene Frequency / genetics
  • Genetic Carrier Screening
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Homozygote
  • Humans
  • Image Interpretation, Computer-Assisted
  • Kruppel-Like Transcription Factors / genetics*
  • Magnetic Resonance Imaging
  • Male
  • Organ Size / physiology
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics*
  • Psychiatric Status Rating Scales
  • Reference Values
  • Schizophrenia / diagnosis
  • Schizophrenia / genetics*
  • Schizophrenic Psychology*
  • Young Adult


  • Kruppel-Like Transcription Factors
  • ZNF804A protein, human