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Genetic association studies of schizophrenia using the 8p21-22 genes: prepronociceptin (PNOC), neuronal nicotinic cholinergic receptor alpha polypeptide 2 (CHRNA2) and arylamine N-acetyltransferase 1 (NAT1)

Abstract

Schizophrenia is a common, genetically heterogeneous disorder with a lifetime prevalence of approximately 1% in the general population. Linkage studies of affected families have now strongly implicated a susceptibility locus on chromosome 8p21-22. Tests of allelic association with markers on 8p21-22 should be able to localise any quantitative trait nucleotides (QTN’s) or susceptibility mutations to within a few hundred kilobases. Three brain expressed candidate susceptibility genes, prepronociceptin (PNOC), neuronal cholinergic receptor, nicotinic, alpha polypeptide 2 (CHRNA2) and arylamine N-acetyltransferase 1 (NAT1) have been mapped to chromosome 8p21-22. A case-control, allelic association study was performed using a novel highly polymorphic dinucleotide repeat, D8S2611 near the PNOC gene, two previously characterised dinucleotide repeats, D8S131 and D8S131P at the CHRNA2 locus and an RFLP at the 3′UTR of the arylamine N-acetyltransferase 1 (NAT1) gene. No differences were found in allele frequencies between the patient and control groups. DNA variations or mutations at or near the three genes under study are unlikely to increase susceptibility to schizophrenia in our population sample.

References

  1. 1

    Brzustowicz LM, Honer WG, Chow EWC, et al. Linkage of familial schizophrenia to chromosome 13q32 Am J Hum Gene 1999 65: 1096–1103

    CAS  Article  Google Scholar 

  2. 2

    Blouin JL, Dombroski BA, Nath SK, et al. Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21 Nature Genet 1998 20: 70–73

    CAS  Article  Google Scholar 

  3. 3

    Gurling HMD, Kalsi G, Brynjolfsson J, et al. Genome-wide linkage analysis confirms the presence of susceptibility loci for schizophrenia on chromosomes 1q32.2, 5q33.2 and 8p21-22 and provides support for linkage to schizophrenia on chromosomes 11q23.3-24 and 20q12.1-11.23 Am J Hum Genet 2001 in press

  4. 4

    Darland T, Heinricher MM, Grandy DK . Orphanin FQ/nociceptin: a role in pain and analgesia, but so much more Trends Neurosci 1998 21: 215–221

    CAS  Article  Google Scholar 

  5. 5

    Freedman R, Coon H, Myles-Worsley M, et al. Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus Proc Nat Acad Sci USA 1997 94: 587–592

    CAS  Article  Google Scholar 

  6. 6

    Wood S, Schertzer M, Yaremko ML . Identification of the human neuronal nicotinic cholinergic alpha 2 receptor locus, (CHRNA2), within an 8p21 mapped locus, by sequence homology with rat DNA Som Cell Mol Genet 1995 21: 147–150

    CAS  Article  Google Scholar 

  7. 7

    Matas N, Thygesen P, Stacey M, Risch A, Sim E . Mapping AAC1, AAC2 and AACP, the genes for arylamine N-acetyltransferases, carcinogen metabolising enzymes on human chromosome 8p22, a region frequently deleted in tumours Cytogenet Cell Genet 1997 77: 290–295

    CAS  Article  Google Scholar 

  8. 8

    Spitzer R, Endicott J, Robins E . Research diagnostic criteria for a selected group of functional disorders, 3rd edition New York: New York State Psychiatric Institute 1978

  9. 9

    McGuffin P, Farmer A, Harvey I . A polydiagnostic application of operational criteria in studies of psychotic illness – development and reliability of the opcrit system Arch Gen Psychiat 1991 48: 764–770

    CAS  Article  Google Scholar 

  10. 10

    Spitzer R, Endicott J . The schedule for affective disorders and schizophrenia, lifetime version, 3rd edition New York: New York State Psychiatric Institute 1977

  11. 11

    Bell DA, Stephens EA, Castranio T, et al. Polyadenylation polymorphism in the acetyltransferase 1 gene (NAT1) increases risk of colorectal cancer Cancer Res 1995 55: 3537–3542

    CAS  PubMed  Google Scholar 

  12. 12

    Payton MA, Sim E . Genotyping human arylamine N-acetyltransferase type 1 (NAT1): the identification of two novel allelic variants Biochem Pharmacol 1998 55: 361–366

    CAS  Article  Google Scholar 

  13. 13

    Sham PC, Curtis D . Monte Carlo tests for associations between disease and alleles at highly polymorphic loci Annals of Human Genetics 1995 59: Pt 1 97–105

    CAS  Article  Google Scholar 

  14. 14

    Terwilliger J, Ott J . Linkage disequilibrium between alleles at marker loci Handbook of Human Genetic Linkage Baltimore: Johns Hopkins University Press 1994

    Google Scholar 

  15. 15

    Ioannou PA, Jong PJ . Construction of Bacterial Artificial Chromosome libraries using the modified P1 (PAC) system In: al. De, ed. Current Protocols in Human Genetics NY: John Wiley and Sons 1996

  16. 16

    Mollereau C, Simons MJ, Soularue P, et al. Structure, tissue distribution, and chromosomal localization of the prepronociceptin gene Proc Nat Acad SCI USA 1996 93: 8666–8670

    CAS  Article  Google Scholar 

  17. 17

    Owen MJ, Holmans P, McGuffin P . Association studies in psychiatric genetics Mol Psychiat 1997 2: 270–273

    CAS  Article  Google Scholar 

  18. 18

    Crowe RR . Candidate genes in psychiatry: an epidemiological perspective [see comments] Am J Med Genet 1993 48: 74–77

    CAS  Article  Google Scholar 

  19. 19

    Wijsman EM . Association vs linkage analysis in mental disorders In: Blum K, Noble E, (eds): Handbook of Psychiatric Genetics 1997

Download references

Acknowledgements

We would like to thank the UK HGMP Resource Center for providing the PAC library. The research was funded by the Neuroscience Research Charitable Trust.

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Correspondence to Hugh MD Gurling.

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Blaveri, E., Kalsi, G., Lawrence, J. et al. Genetic association studies of schizophrenia using the 8p21-22 genes: prepronociceptin (PNOC), neuronal nicotinic cholinergic receptor alpha polypeptide 2 (CHRNA2) and arylamine N-acetyltransferase 1 (NAT1). Eur J Hum Genet 9, 469–472 (2001). https://doi.org/10.1038/sj.ejhg.5200646

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Keywords

  • polymorphism
  • D8S2611
  • neuropeptides
  • neuronal acetylcholine receptor
  • candidate gene
  • schizophrenia

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