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:

A genome-wide search for quantitative trait loci underlying asthma

Abstract

ASTHMA now affects one child in seven in the United Kingdom1. Most cases (95%) of childhood asthma are associated with atopy, the immunoglobulin E (IgE)-mediated familial syndrome of allergic asthma, eczema and rhinitis. Segregation analysis has consistently suggested the presence of major genes influencing atopy and IgE levels2–4, with the expectation that these genes may be identified by positional cloning or the examination of candidate genes. Here we report the results of a genome-wide search for linkage to one qualitative and four quantitative traits associated with allergic (atopic) asthma. We have identified six potential linkages (P < 0.001), five of which are to quantitative traits. Monte Carlo simulations show that 1.6 false-positive linkages at this level of significance would be expected from the data. One linkage, to chromosome Ilql3, has been established previously5. Three of the new loci show evidence of linkage to a second panel of families, in which maternal effects and pleiotropy of linked phenotypes are seen. The results demonstrate the extent and the complexity of the genetic predisposition to asthma.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

  1. Strachan, D. P., Anderson, H. R., Limb, E. S., O'Neill, A. & Wells, N. Arch. Dis. Child. 70, 174–178 (1994).

    Article  CAS  Google Scholar 

  2. Gerrard, J. W., Rao, D. C. & Morton, N. E. Am. J. Hum. Genet. 30, 46–58 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Borecki, I., Rao, D. C., Lalouel, J. M., McGue, L. & Gerrard, J. W. Genet. Epidemiol. 2, 327–338 (1985).

    Article  CAS  Google Scholar 

  4. Dizier, M. H. et al. Genet. Epidemiol. 12, 93–105 (1995).

    Article  CAS  Google Scholar 

  5. Sandford, A. J. et al. Lancet 341, 332–334 (1993).

    Article  CAS  Google Scholar 

  6. O'Connor, G. T. & Weiss, S. T. Am. J. Respir. Crit. Care Med. 149, S21–28 (1994).

    Article  CAS  Google Scholar 

  7. Holford-Strevens, V. et al. J. Allergy Clin. Immunol. 73, 516–522 (1984).

    Article  CAS  Google Scholar 

  8. Peat, J. K., Brittoh, W. J., Salome, C. M. & Woolcock, A. J. Clin. Allergy 17, 271–281 (1987).

    Article  Google Scholar 

  9. Cline, M. G. & Burrows, B. B. Thorax 44, 425–432 (1989).

    Article  CAS  Google Scholar 

  10. Moffatt, M. F. et al. Clin. Exp. Allergy 22, 1046–1051 (1992).

    Article  CAS  Google Scholar 

  11. O'Connor, G., Sparrow, D., Taylor, D., Segal, M. & Weiss, S. Am. Rev. Respir. Dis. 136, 1412–1417 (1987).

    Article  CAS  Google Scholar 

  12. Cookson, W. O. C. M. & Hopkin, J. M. Lancet (i), 86–88 (1988).

  13. Young, R. P. et al. J. Med. Genet. 29, 236–238 (1992).

    Article  CAS  Google Scholar 

  14. Haseman, J. K. & Elston, R. C. Behav. Genet 2, 3–19 (1972).

    Article  CAS  Google Scholar 

  15. Reed, P. W. et al. Nature Genet 7, 390–395 (1994).

    Article  CAS  Google Scholar 

  16. Weissenbach, J. et al. Nature 359, 794–801 (1992).

    Article  ADS  CAS  Google Scholar 

  17. Magnusson, C. G. Allergy 43, 241–251 (1988).

    Article  CAS  Google Scholar 

  18. Halonen, M. et al. Am. Rev. Respir. Dis. 146, 866–870 (1992).

    Article  CAS  Google Scholar 

  19. Åberg, N. Clin. Exp. Allergy 23, 829–834 (1994).

    Article  Google Scholar 

  20. Kuehr, J. et al. Clin. Exp. Allergy 23, 600–605 (1993).

    Article  CAS  Google Scholar 

  21. Cookson, W. O. C. M., Sharp, P. A., Faux, J. A. & Hopkin, J. M. Lancet (i), 1292–1295 (1989).

  22. Shirakawa, T. et al. Clin. Genet 46, 125–129 (1994).

    Google Scholar 

  23. Collée, J. M. et al. Lancet 341, 936 (1993).

    Article  Google Scholar 

  24. Herwerden, L. et al. Lancet 346, 1262–1265 (1995).

    Article  Google Scholar 

  25. Eiberg, H., Lind, P., Mohr, J. & Nielsen, L. S. Cytogenet. Cell. Genet. 40, 622 (1985).

    Google Scholar 

  26. Marsh, D. G. et al. Science 264, 1152–1155 (1994).

    Article  ADS  CAS  Google Scholar 

  27. Myers, D. A. et al. Genomics 23, 464–470 (1994).

    Article  Google Scholar 

  28. Suarez, B. K., Hampe, C. L. & Van Eerdewegh, P. in Genetic Approaches to Mental Disorders (eds Gershon, E. S. & Cloninger, C. R.) 23–46 (American Psychiatric, Washington DC, 1994).

    Google Scholar 

  29. Hill, M. R. et al. BMJ 311, 776–779 (1995).

    Article  CAS  Google Scholar 

  30. Hodge, S. E. Genet. Epidemiol. 1, 109–122 (1984).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Daniels, S., Bhattacharrya, S., James, A. et al. A genome-wide search for quantitative trait loci underlying asthma. Nature 383, 247–250 (1996). https://doi.org/10.1038/383247a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/383247a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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