J Med Genet 41:31-34 doi:10.1136/jmg.2003.014977
  • Letters to JMG

A case control and family based association study of the neuregulin1 gene and schizophrenia

  1. X Zhao1,2,
  2. Y Shi1,2,
  3. J Tang1,2,
  4. R Tang1,2,
  5. L Yu1,2,
  6. N Gu3,
  7. G Feng3,
  8. S Zhu4,
  9. H Liu4,
  10. Y Xing5,
  11. S Zhao5,
  12. H Sang6,
  13. Y Guan6,
  14. D St Clair7,
  15. L He1,2
  1. 1Bio-X Life Science Research Center, Shanghai Jiao Tong University, Shanghai, China
  2. 2Institute of Nutrition Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
  3. 3Shanghai Institute of Mental Health, Shanghai, China
  4. 4JiLin Institute of Mental Health, JiLin, China
  5. 5Xi’an Institute of Mental Health, Xi’an, China
  6. 6Changchun Kaixuan Hospital, Changchun, China
  7. 7Department of Mental Health, University of Aberdeen, Aberdeen, UK
  1. Correspondence to:
 L He
 Shanghai Jiao Tong University, Bio-X Life Science Research Center, PO Box 501, Hao Ran Building, 1954 Hua Shan Road, Shanghai 200030, China;
  • Accepted 26 October 2003
  • Revised 26 September 2003

Data from twin, family, and adoption studies provide strong evidence that genetic factors play a major aetiological role in schizophrenia. By a series of linkage studies, chromosome 8p has been implicated as a region harbouring a schizophrenia susceptibility gene.1–4 Recently, Stefansson and colleagues reported that neuregulin 1 (NRG1), located in 8p21-12, may be involved in the aetiology of schizophrenia.4,5 In their linkage and association studies, a 290 kb core at risk haplotype at the 5′ end of NRG1 was found to be strongly associated with schizophrenia in Icelandic and Scottish populations. This haplotype contains the first exon of NRG1, which encodes a part of glial growth factor 2 (GGF2). Deficiency of glial growth factors has been presumed to be implicated in the pathogenesis of schizophrenia.6 Futhermore, NRG1 mutant mice have fewer functional N-methyl D-aspartate(NMDA) receptors than wild type mice, and display stereotypic behavioural abnormalities similar to those of normal mice treated with the psychogenic drug phenylcyclidine.4

This core at risk haplotype was defined by five single nucleotide polymorphisms (SNP8NRG221132, SNP8NRG221533, SNP8NRG241930, SNP8NRG243177, SNP8NRG433E1006) and two microsatellites (478B14-848, 420M91395). The frequency of this haplotype in schizophrenic individuals was higher than in controls; in Icelandic samples the frequency was 15.4 (7.5%; p  =  0.000087).4 The first replication using Scottish samples revealed a similar result at 10.2 (5.9%; p  =  0.00031).5 Another replication performed by Williams et al with British or Irish samples used one SNP and the two microsatellites of the core at risk haplotype. However, the association was much weaker at 9.5 (7.5%; p  =  0.04).7 Yang et al reported other markers located in the middle of NRG1 and associated with schizophrenia, in a Chinese population.8 Another independent analysis using 13 microsatellites found two groups of haplotypes, which were significantly …