Genetic association between NRG1 and schizophrenia, major depressive disorder, bipolar disorder in Han Chinese population

Am J Med Genet B Neuropsychiatr Genet. 2016 Apr;171B(3):468-78. doi: 10.1002/ajmg.b.32428. Epub 2016 Feb 17.

Abstract

Schizophrenia, major depressive disorder, and bipolar disorder are three major psychiatric disorders affecting around 0.66%, 3.3%, and 1.5% of the Han Chinese population respectively. Several genetic linkage analyses and genome wide association studies identified NRG1 as a susceptibility gene of schizophrenia, which was validated by its role in neurodevelopment, glutamate, and other neurotransmitter receptor expression regulation. To further investigate whether NRG1 is a shared risk gene for major depressive disorder, bipolar disorder as well as schizophrenia, we performed an association study among 1,248 schizophrenia cases, 1,056 major depression cases, 1,344 bipolar disorder cases, and 1,248 controls. Totally 15 tag SNPs were genotyped and analyzed, and no population stratification was found in our sample set. Among the sites, rs4236710 (corrected Pgenotye = 0.015) and rs4512342 (Pallele = 0.03, Pgenotye = 0.045 after correction) were associated with schizophrenia, and rs2919375 (corrected Pgenotye = 0.004) was associated with major depressive disorder. The haplotype rs4512342-rs6982890 showed association with schizophrenia (P = 0.03 for haplotype "TC" after correction), and haplotype rs4531002-rs11989919 proved to be a shared risk factor for both major depressive disorder ("CC": corrected P = 0.009) and bipolar disorder ("CT": corrected P = 0.003). Our results confirmed that NRG1 was a shared common susceptibility gene for major mental disorders in Han Chinese population.

Keywords: NRG1; association study; bipolar disorder; major depressive disorder; schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian Continental Ancestry Group / genetics*
  • Bipolar Disorder / genetics*
  • Case-Control Studies
  • Depressive Disorder, Major / genetics*
  • Ethnic Groups / genetics*
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Haplotypes / genetics
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Neuregulin-1 / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Schizophrenia / genetics*

Substances

  • NRG1 protein, human
  • Neuregulin-1