Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib–pair linkage analysis

Abstract

The influence of genetic factors in schizophrenia has been convincingly demonstrated by family, twin and adoption studies1–3, but the mode of transmission remains uncertain. The reported pattern of recurrence risks suggests a set of interacting loci4. Based on prior evidence for linkage on chromosome 6p (K. Kendler, pers. comm.), we have scanned the short arm of chromosome 6 in 54 families for loci predisposing to schizophrenia, using 25 microsatellite markers spanning 60 centiMorgans (cM). Allele sharing identity by descent was examined in affected sib-pairs from these families, followed by multipoint sib-pair linkage analysis. Positive lod scores were obtained over a wide region (D6S470 to D6S271), with a maximum lod score of 2.2 occuring near D6S274, located in 6p22. However, we obtained a lod score of −2 at D6S296, the locus found by others to provide the greatest linkage evidence5. At D6S274, we report a positive lod score as do Straub et al.5 (individually non-significant). A combined total lod of 3.6–4.0 suggests the possibility of a susceptibility locus in this region. However, methodological differences between our studies makes a firm conclusion difficult.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Bertelsen, A. Controversies and consistencies in psychiatric genetics. Acta Psychiat. Scand. 71, 61–75 (1985).

    Article  Google Scholar 

  2. Kendler, K.S. Familial aggregation of schizophrenia and schizophrenia spectrum disorders. Arch. gen. Psychiat. 45, 377–383 (1988).

    Article  CAS  PubMed  Google Scholar 

  3. Gottesmann, I.I. & Bertelsen, A. Confirming unexpressed genotypes for schizophrenia: risks in the offspring of Fischers identical and fraternal discordant twins. Arch. gen. Psychiat. 46, 867–872 (1989).

    Article  Google Scholar 

  4. Risch, N. Linkage strategies for genetically complex traits. I. multilocus models. Am. J. hum. Genet. 46, 229–241 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Straub, R. et al. A potential vulnerability locus for schizophrenia on chromosome 6p24–22: evidence for genetic heterogeneity. Nature Genet. 11, 287–293 (1995).

    Article  CAS  PubMed  Google Scholar 

  6. Gyapay, G. et al. The 1993–94 Généthon human genetic linkage map. Nature Genet. 7, 246–339 (1994).

    Article  CAS  PubMed  Google Scholar 

  7. Risch, N. Linkage strategies for genetically complex traits. II. the power of affected relative pairs. Am. J. hum. Genet. 46, 229–241 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Risch, N. Exclusion mapping for complex diseases. Am. J. hum. Genet. 53, A185 (1993).

    Google Scholar 

  9. Maier, W. et al. Continuity and discontinuity of affective disorders and schizophrenia. Results of a controlled family study. Arch. gen. Psychiat. 50, 871–883 (1993).

    Article  CAS  PubMed  Google Scholar 

  10. Penrose, L.S. The general purpose sib-pair linkage test. Ann. Eugen. 18, 120–124 (1953).

    Article  CAS  PubMed  Google Scholar 

  11. Suarez, B.K. & Van Erdewegh, P. A comparison of three affected-sib-pair scoring method to detect HLA-linked disease susceptibility genes. Am. J. med. Genet. 18, 135–146 (1984).

    Article  CAS  PubMed  Google Scholar 

  12. Knapp, M., Seuchter, S.A. & Baur, M.P. Linkage analysis in nuclear families, 1: Optimality criteria for affected sib-pair tests. Hum. Hered. 44, 37–43 (1994).

    Article  CAS  PubMed  Google Scholar 

  13. Knapp, M., Seuchter, S.A. & Baur, M.R. Linkage analysis in nuclear families, 2: relationship between affected sib-pair tests and lod score analysis. Hum. Hered. 44, 44–51 (1994).

    Article  CAS  PubMed  Google Scholar 

  14. Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Multilocus linkage analysis in humans: detection of linkage and estimation of recombination. Am. J. hum. Genet. 37, 482–498 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Polymeropoulos, M.H., Rath, D.S., Xiao, H. & Merril, T.R. Tetranucleotide repeat polymorphism at the human coagulation factor XIIIA subunit gene (F13A1). Nucl. Acids Res. 19, 4306 (1991).

    PubMed  PubMed Central  Google Scholar 

  16. Macaubas, C., Hallmayer, J., Kalil, J., Grumet, C. & Mignot, E. Extensive polymorphism of a (CA)n microsatellite located in the HLA-DQA1/DQB1 class II region. Hum. Immunol. 42, 209–220 (1995).

    Article  CAS  PubMed  Google Scholar 

  17. Wang, S. et al. Evidence for a susceptibility locus for schizophrenia on chromosome 6pter–p22. Nature Genet. 10, 41–46 (1995).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schwab, S., Albus, M., Hallmayer, J. et al. Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib–pair linkage analysis. Nat Genet 11, 325–327 (1995). https://doi.org/10.1038/ng1195-325

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1195-325

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing