Identification of a novel neuregulin 1 at-risk haplotype in Han schizophrenia Chinese patients, but no association with the Icelandic/Scottish risk haplotype (original) (raw)

Molecular Psychiatry volume 9, pages 698–704 (2004)Cite this article

Abstract

To determine if neuregulin 1 (NRG1) is associated with schizophrenia in Asian populations, we investigated a Han Chinese population using both a family trio design and a case–control design. A total of 25 microsatellite markers and single nucleotide polymorphisms (SNPs) were genotyped spanning the 1.1 Mb NRG1 gene including markers of a seven-marker haplotype at the 5′end of the gene found to be in excess in Icelandic and Scottish schizophrenia patients. The alleles of the individual markers forming the seven marker at-risk haplotype are not likely to be causative as they are not in excess in patients in the Chinese population studied here. However using unrelated patients, we find a novel haplotype (HAPChina 1), immediately upstream of the Icelandic haplotype, in excess in patients (11.9% in patients vs 4.2% in controls; _P_=0.0000065, risk ratio (rr) 3.1), which was not significant when parental controls were used. Another haplotype (HAPChina 2) overlapping the Icelandic risk haplotype was found in excess in the Chinese (8.5% of patients vs 4.0% of unrelated controls; _P_=0.003, rr 2.2) and was also significant using parental controls only (_P_=0.0047, rr 2.1). A four-marker haplotype at the 3′ end of the NRG1 gene, HAPChina 3, was found at a frequency of 23.8% in patients and 13.7% in nontransmitted parental haplotypes (_P_=0.000042, rr=2.0) but was not significant in the case–control comparison. We conclude that different haplotypes within the boundaries of the NRG1 gene may be associated with schizophrenia in the Han Chinese.

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Acknowledgements

This work was partly funded by NSFC (China), NARSAD, the Psychiatry Research Trust and the Wellcome Trust.

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Authors and Affiliations

  1. Division of Psychological Medicine, Institute of Psychiatry, London, UK
    T Li, R M Murray, D Januel & D A Collier
  2. West China Hospital, Sichuan University, PR, China
    T Li, G Cai & X Liu
  3. Decode Genetics, Reykjavík, Iceland
    H Stefansson, E Gudfinnsson, V Steinthorsdottir, V G Gudnadottir, A Ingason, J R Gulcher & K Stefansson
  4. Division of Psychiatry, Landspitali University Hospital, Reykjavík, Iceland
    H Petursson

Authors

  1. T Li
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  2. H Stefansson
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  3. E Gudfinnsson
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  4. G Cai
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  5. X Liu
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  6. R M Murray
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  7. V Steinthorsdottir
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  8. D Januel
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  9. V G Gudnadottir
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  10. A Ingason
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  11. J R Gulcher
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  12. K Stefansson
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  13. D A Collier
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Corresponding author

Correspondence toD A Collier.

Additional information

Electronic-database information

Accession Numbers and URLs for data in this article are as follows:

deCODE genetics http://www.decode.com/nrg1/markers for SNPs and microsatellite markers in the NRG1 locus sequence;

GenBank, http://www.ncbi.nlm.nih.gov/Genbank/ for NRG1 (AF491780);

Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim (for NRG1 (MIM 142445), SCZD (MIM 181500) and SCZD6 (MIM 603013));

Third Party Annotation, DDBJ/EMBL/GenBank databases for NRG1 (TPA: BK000383).

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Li, T., Stefansson, H., Gudfinnsson, E. et al. Identification of a novel neuregulin 1 at-risk haplotype in Han schizophrenia Chinese patients, but no association with the Icelandic/Scottish risk haplotype.Mol Psychiatry 9, 698–704 (2004). https://doi.org/10.1038/sj.mp.4001485

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