Human Molecular Genetics Advance Access published online on May 10, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl122
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Bio-X Center, Shanghai Jiao Tong University, Shanghai 200030, China; Institute for Nutritional sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
* To whom correspondence should be addressed. Chromosome 8p22-p11 has been identified as a locus for schizophrenia in several genome-wide scans and confirmed by meta-analysis of published linkage data. Systematic fine mapping using extended Icelandic pedigrees identified an associated haplotype in the gene neuregulin 1 (NRG1), also known as heuregulin, glial growth factor, NDF43 and ARIA. A 290 kb core at risk haplotype at the 5' end of the gene (HAPICE), defined by five SNPs and two microsatellite polymorphisms was found to be associated with schizophrenia in the Icelandic and Scottish populations. A number of subsequent independent studies have attempted to replicate the association, and while some have been successful, the associated haplotype is not always HAPICE. Furthermore no obviously functional or pathogenic variants have been identified, and the relationship between the gene and schizophrenia has remained inconclusive. To reconcile these conflicting findings and to give a comprehensive picture of the genetic architecture of this important gene, we performed a meta-analysis of thirteen published population-based and family-based association studies up to November 2005. We analysed data from the SNP markers SNP8NRG241930, SNP8NRG243177, SNP8NRG221132 and SNP8NRG221533, and the microsatellite markers 478B14-848, 420M9-1395. Across these studies, strong positive association was found for all six polymorphisms. The haplotype analysis also showed significant association in the pooled international populations (OR=1.22, 95% C.I. 1.15 - 1.3, p=8x10-10). In Asian populations the risk haplotype was focused around the two microsatellite markers, 478B14-848, 420M9-1395 (haplotype block B), and in Caucasian populations with the remaining four SNP markers (haplotype block A). This meta-analysis supports the involvement of NRG1 in the pathogenesis of schizophrenia, but with association between two different but adjacent haplotypes blocks in the Caucasian and Asian populations.
Received March 10, 2006
Revised May 3, 2006
Accepted May 3, 2006
Article
Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia
Dawei Li 1,
David A Collier 2,
and
Lin He 3 *
2 Division of Psychological Medicine and MRC Social Genetic and Developmental Psychiatry Centre, The Institute of Psychiatry, King's College London
3 Institute for Nutritional sciences, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China; NHGG, Bio-X Center, Shanghai Jiaotong University, Hao Ran Building, 1954 Hua Shan Road, Shanghai 200030, China
Lin He, E-mail: helin{at}nhgg.org
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Alaerts, S. Ceulemans, D. Forero, L. N. Moens, S. De Zutter, L. Heyrman, A.-S. Lenaerts, K.-F. Norrback, P. De Rijk, L.-G. Nilsson, et al. Support for NRG1 as a Susceptibility Factor for Schizophrenia in a Northern Swedish Isolated Population Arch Gen Psychiatry, August 1, 2009; 66(8): 828 - 837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Fisahn, J. Neddens, L. Yan, and A. Buonanno Neuregulin-1 Modulates Hippocampal Gamma Oscillations: Implications for Schizophrenia Cereb Cortex, March 1, 2009; 19(3): 612 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Wood, F. Bonath, S. Kumar, C. A. Ross, and V. T. Cunliffe Disrupted-in-schizophrenia 1 and neuregulin 1 are required for the specification of oligodendrocytes and neurones in the zebrafish brain Hum. Mol. Genet., February 1, 2009; 18(3): 391 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. B. Kwon, D. Paredes, C. M. Gonzalez, J. Neddens, L. Hernandez, D. Vullhorst, and A. Buonanno Neuregulin-1 regulates LTP at CA1 hippocampal synapses through activation of dopamine D4 receptors PNAS, October 7, 2008; 105(40): 15587 - 15592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Bray, P. A. Holmans, M. B. van den Bree, L. Jones, L. A. Elliston, G. Hughes, A. L. Richards, N. M. Williams, N. Craddock, M. J. Owen, et al. Cis- and trans- loci influence expression of the schizophrenia susceptibility gene DTNBP1 Hum. Mol. Genet., April 15, 2008; 17(8): 1169 - 1174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Tan, Y. Wang, B. Gold, J. Chen, M. Dean, P. J. Harrison, D. R. Weinberger, and A. J. Law Molecular Cloning of a Brain-specific, Developmentally Regulated Neuregulin 1 (NRG1) Isoform and Identification of a Functional Promoter Variant Associated with Schizophrenia J. Biol. Chem., August 17, 2007; 282(33): 24343 - 24351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Li and L. He G72/G30 Genes and Schizophrenia: A Systematic Meta-analysis of Association Studies Genetics, February 1, 2007; 175(2): 917 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Li, P. C. Sham, M. J. Owen, and L. He Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD) Hum. Mol. Genet., July 15, 2006; 15(14): 2276 - 2284. [Abstract] [Full Text] [PDF]
|
|