Effects of genetic variations in NRG1 on cognitive domains in patients with schizophrenia and healthy individuals

Psychiatr Genet. 2015 Aug;25(4):147-54. doi: 10.1097/YPG.0000000000000087.


Background: The neuregulin 1 (NRG1) gene has been investigated as a candidate susceptibility gene for schizophrenia. A number of studies have also explored the genetic effect of NRG1 on cognitive deficits related to schizophrenia, and thus far generated inconsistent results. The current study aimed to determine whether genetic variations in NRG1 are associated with cognitive domains in schizophrenic patients and healthy individuals.

Materials and methods: Comprehensive neuropsychological tests composed of six cognitive domains were administered to 135 clinically stable patients with schizophrenia and 119 healthy individuals. On the basis of previous reports of positive association, a total of four single nucleotide polymorphisms were analyzed. In testing the genotype effect on cognitive domains, we used repeated-measure analysis for six cognitive domain scores of each individual as repeated measurements.

Results: An association of P-value less than 0.05 with at least one cognitive domain in patients and/or healthy individuals was observed for all of the single nucleotide polymorphisms. After applying the correction for multiple testing, the association remained statistically significant between rs6994992 and general cognitive ability (g) in the patient group and between rs2439272 and the 'working memory' domain in the group of healthy participants.

Conclusion: This study suggests the involvement of NRG1 in the susceptibility for developing cognitive deficits in schizophrenic patients. For some cognitive domains, its genetic effect was also significant in generating interindividual variability within the normal functional range.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cognition Disorders / genetics
  • Cognition Disorders / psychology
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Neuregulin-1 / genetics*
  • Neuropsychological Tests
  • Polymorphism, Single Nucleotide
  • Republic of Korea
  • Schizophrenia / diagnosis
  • Schizophrenia / genetics*


  • NRG1 protein, human
  • Neuregulin-1