Polymorphisms in NRGN are associated with schizophrenia, major depressive disorder and bipolar disorder in the Han Chinese population

J Affect Disord. 2016 Apr;194:180-7. doi: 10.1016/j.jad.2016.01.034. Epub 2016 Jan 13.

Abstract

Background: The NRGN gene locates on 11q24 and encodes a postsynaptic protein kinase substrate that binds calmodulin in the absence of calcium. In a previous genome-wide association study of schizophrenia in the Caucasian population, rs12807809 of NRGN was found to be significantly associated with schizophrenia, moreover, it was further found to be associated with bipolar disorder.

Methods: We recruited 1248 schizophrenia cases, 1344 bipolar disorder cases, 1056 major depressive disorder cases, and 1248 healthy controls from Han Chinese population. Rs12807809 and another two tag SNPs of NRGN were genotyped and analyzed in three diseases respectively. A meta-analysis of rs12807809 was also conducted to verify its association with schizophrenia in Han Chinese population.

Results: Rs7113041 was associated with bipolar disorder (odds ratio, 95% confidence interval (OR, 95% CI)=1.194, 1.032-1.383; Pgenotype=0.0126), and rs12278912 was associated with major depressive disorder (OR, 95% CI=0.789, 0.673-0.924; Pallele=0.0102, Pgenotype=0.0399) after Bonferroni correction. The "GA" haplotype of rs7113041-rs12278912 was significantly associated with schizophrenia, major depressive disorder and bipolar disorder (corresponding P values were 2.85E-04, 3.00E-03, and 5.40E-04 after Bonferroni correction).

Limitations: Despite the association between NRGN and psychoses we have found, we failed to validate the positive variant rs12807809, which was reported in the Caucasian genome-wide association study both in our single site association test and the meta-analysis. Functional studies are needed to illuminate the role of NRGN in the pathogenesis of these mental disorders.

Conclusions: Our findings prove that NRGN is a shared susceptibility gene of schizophrenia, major depression and bipolar disorder in Han Chinese, and this might provide a new target for the diagnosis and treatment of these mental disorders.

MeSH terms

  • Adult
  • Asian Continental Ancestry Group / genetics*
  • Asian Continental Ancestry Group / statistics & numerical data
  • Bipolar Disorder / genetics*
  • Case-Control Studies
  • Depressive Disorder, Major / genetics*
  • Female
  • Genetic Predisposition to Disease / ethnology*
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Neurogranin / genetics*
  • Polymorphism, Single Nucleotide*
  • Schizophrenia / genetics*

Substances

  • NRGN protein, human
  • Neurogranin