The study investigated the possible association of NRG3 gene and schizophrenia in a Han Chinese population.
Of a total of 1345, 270 unrelated schizophrenia inpatients, 235 normal control subjects, and 280 nuclear families (trios) with schizophrenia probands were studied. Nine single nucleotide polymorphisms (SNPs) spanning intron 1 to exon 9 of the NRG3 gene were analyzed, starting with the case-control samples. The SNPs showing significant association with schizophrenia in the case-control samples were subsequently studied in the independent trio samples with family-based association analysis.
In case-control samples, two SNPs (rs1937970 and rs677221) showed significant genotypic and allelic association with schizophrenia (all p < .05) with rs677221-C being the risk allele for schizophrenia (uncorrected p = .001, odds ratio = 1.439, 95% confidence interval = 1.115–1.858). Haplotypes GC constructed by the two SNPs was also significantly associated with schizophrenia (permutation p value = .0047). In the independent trio samples, rs1937970-A and rs677221-G consistently showed significant under-transmission to schizophrenic offspring (unadjusted p = .003 and p = .004, respectively). In the haplotype–transmission disequilibrium test (TDT) for allelic combination of rs1937970-rs677221, significant under-transmission for haplotype AG (uncorrected p = .006) and over-transmission for haplotype GC (uncorrected p = .004) to the affected schizophrenia offspring were observed.
The result supports that the NRG3 gene is a susceptibility gene for schizophrenia.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Biological Psychiatry
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Neuregulin and ErbB receptor signaling pathways in the nervous system.Curr Opin Neurobiol. 2001; 11: 287-296
- Neuregulin 1 and susceptibility to schizophrenia.Am J Hum Genet. 2002; 71: 877-892
- Association of neuregulin 1 with schizophrenia confirmed in a Scottish population.Am J Hum Genet. 2003; 72: 83-87
- Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia.Hum Mol Genet. 2006; 15: 1995-2002
- Association of the NRG1 gene and schizophrenia: A meta-analysis.Mol Psychiatry. 2006; 11: 539-546
- Neuregulin 1 genotype and schizophrenia.Schizophr Bull. 2008; 34: 9-12
- Neuregulin-3 (NRG3): A novel neural tissue-enriched protein that binds and activates ErbB4.Proc Natl Acad Sci U S A. 1997; 94: 9562-9567
- Disease-associated intronic variants in the ErbB4 gene are related to altered ErbB4 splice-variant expression in the brain in schizophrenia.Hum Mol Genet. 2007; 16: 129-141
- Further evidence for association between ErbB4 and schizophrenia and influence on cognitive intermediate phenotypes in healthy controls.Mol Psychiatry. 2006; 11: 1062-1065
- The involvement of ErbB4 with schizophrenia: Association and expression studies.Am J Med Genet B Neuropsychiatr Genet. 2006; 141: 142-148
- Human NRG3 gene Map position 10q22-q23.Chromosome Res. 2000; 8: 560
- Genomewide linkage scan for schizophrenia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 10q22.Am J Hum Genet. 2003; 73: 601-611
- Genome scan of Han Chinese schizophrenia families from Taiwan: Confirmation of linkage to 10q22.3.Am J Psychiatry. 2006; 163: 1760-1766
- PLINK: A tool set for whole-genome association and population-based linkage analyses.Am J Hum Genet. 2007; 81: 559-575
- A direct approach of false discovery rates.J R Stat Soc Ser B. 2002; 64: 479-498
- Bipolar I disorder and schizophrenia: A 440-single-nucleotide polymorphism screen of 64 candidate genes among Ashkenazi Jewish case-parent trios.Am J Hum Genet. 2005; 77: 918-936
- Interactions among genes in the ErbB-Neuregulin signalling network are associated with increased susceptibility to schizophrenia.Behav Brain Funct. 2007; 3: 31
- Transmission test for linkage disequilibrium: The insulin gene region and insulin-dependent diabetes mellitus (IDDM).Am J Hum Genet. 1993; 52: 506-516
- Spurious genetic associations.Biol Psychiatry. 2007; 61: 1121-1126
Published online: August 19, 2008
Accepted: July 9, 2008
Received in revised form: July 8, 2008
Received: April 10, 2008
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.