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.

  • Full Paper
  • Published:

Linkage analysis of susceptibility to leprosy type using an IBD regression method

Genes & Immunity volume 5, pages 221–225 (2004)Cite this article

Abstract

Leprosy is a chronic disease caused by infection with Mycobacterium leprae, which is manifested across a wide clinical spectrum. There is evidence that susceptibility both to leprosy per se and to the clinical type of leprosy is influenced by host genetic factors. This paper describes the application of an identity by descent regression search for genetic determinants of leprosy type among families from Karonga District, Northern Malawi. Suggestive evidence was found for linkage to leprosy type on chr 21q22 (P<0.001). The methodological implications of the approach and the findings are discussed.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2

Similar content being viewed by others

References

  1. WHO. Leprosy global situation. Weekly Epidemiol Rec 2002; 77: 1–8.

  2. Bryceson A, Pfaltzgraff RE . Leprosy 1990;Churchill Livingstone: New York.

    Google Scholar 

  3. Mira MT, Alcas A, Thuc NV et al. Chromosome 6q25 is linked to susceptibility to leprosy in a Vietnamese population. Nat Genet 2003; 21: 412–415.

    Article  Google Scholar 

  4. Tosh K, Meisner S, Siddiqui R et al. A region of chromosome 20 is linked to leprosy susceptibility in a South Indian population. J Infect Dis 2002; 186: 1190–1193.

    Article  CAS  Google Scholar 

  5. Siddiqui R, Meisner S, Tosh K et al. A major susceptibility locus for leprosy in India maps to chromosome 10p13. Nat Genet 2001; 27: 439–441.

    Article  CAS  Google Scholar 

  6. Blackwell JM . Modern genetics and leprosy susceptibility. Lepr Rev 2001; 72: 352–356.

    CAS  PubMed  Google Scholar 

  7. Shaw M, Donaldson IJ, Collins A et al. Association and linkage of leprosy phenotypes with HLA class II and tumour necrosis factor genes. Genes Immun 2001; 2: 196–204.

    Article  CAS  Google Scholar 

  8. Roy S, Frodsham A, Hazra SK, Mascie-Taylor CGN, Hill AVS . Association of vitamin D receptor genotype with leprosy type. J Infect Dis 1999; 179: 187–191.

    Article  CAS  Google Scholar 

  9. Van Eden W, Gonzalez NM, de Vries RRP, Convit J, van Rood JJ . HLA-linked control of predisposition to lepromatous leprosy. J Infect Dis 1985; 151: 9–14.

    Article  CAS  Google Scholar 

  10. van Eden W, de Vries RRP, Mehra NK, Vaidya MC, D'Amaro J, van Rood JJ . HLA segregation of tuberculoid leprosy: confirmation of the DR2 marker. J Infect Dis 1980; 141: 693–701.

    Article  CAS  Google Scholar 

  11. Abel L, Sánchez FA, Oberti J et al. Susceptibility to leprosy is linked to the human NRAMP1 gene. J Infect Dis 1998; 177: 133–145.

    Article  CAS  Google Scholar 

  12. Meisner SJ, Mucklow S, Warner G, Sow SO, Lienhardt C, Hill AVS . Association of NRAMP1 polymorphism with leprosy type but not susceptibility to leprosy per se in West Africans. Am J Trop Med Hyg 2001; 65: 733–735.

    Article  CAS  Google Scholar 

  13. Santos AR, Almeida AS, Suffys PN et al. Tumor necrosis factor promoter polymorphism (TNF2) seems to protect against development of severe forms of leprosy in a pilot study in Brazilian patients. Int J Lepr Other Mycobact Dis 2000; 68: 325–327.

    CAS  PubMed  Google Scholar 

  14. Roy S, McGuire W, Mascie-Taylor C et al. Tumor necrosis factor promoter polymorphism and susceptibility to lepromatous leprosy. J Infect Dis 1997; 176: 530–532.

    Article  CAS  Google Scholar 

  15. Shaw MA, Collins A, Peacock CS et al. Evidence that genetic susceptibility to Mycobacterium tuberculosis in a Brazilian population is under oligogenic control: linkage study of the candidate genes NRAMP1 and TNFA. Tubercle Lung Dis 1997; 78: 35–45.

    Article  CAS  Google Scholar 

  16. Job CK . Genetics and leprosy. Lepr India 1980; 152: 353–358.

    Google Scholar 

  17. Fine PEM . Implications of genetics for the epidemiology and control of leprosy. Phil Trans R Soc Lond Ser B 1988; 321: 365–376.

    Article  CAS  Google Scholar 

  18. Pönnighaus J, Fine PE, Bliss L et al. The Lepra Evaluation Project (LEP) and epidemiological study of leprosy in northern Malawi. I: methods. Lepr Rev 1987; 52: 359–375.

    Google Scholar 

  19. Fitness J, Siddiqui R, Wallace C et al. No evidence for a major locus for leprosy susceptibility on chr10p13 in Karonga District, Malawi. (in preparation) .

  20. Holmans P . Detecting gene-gene interactions using affected sib pair analysis with covariates. Hum Hered 2002; 53: 92–102.

    Article  Google Scholar 

  21. Hogg N, Stewart MP, Scarth SL et al. A novel leukocyte adhesion deficiency caused by expressed but nonfunctional β2 integrins Mac-1 and LFA-1. J Clin Invest 1999; 103: 97–106.

    Article  CAS  Google Scholar 

  22. Casanova J-L, Abel L . Genetic disection of immunity to mycobacteria: the human model. Annu Rev Immunol 2002; 20: 581–620.

    Article  CAS  Google Scholar 

  23. Fitness J, Tosh K, Hill AVS . Genetics of susceptibility to leprosy. Genes Immun 2002; 3: 441–453.

    Article  CAS  Google Scholar 

  24. Pönnighaus JM, Fine PEM, Bliss L . Certainty levels in the diagnosis of leprosy. Int J Lepr Other Mycobact Dis 1987; 55: 454–462.

    PubMed  Google Scholar 

  25. Rice JP, Rochberg N, Neuman RJ et al. Covariates in linkage analysis. Genet Epidemiol 1999; 17: S691–S695.

    Article  Google Scholar 

  26. Huber PJ . The behaviour of maximum likelihood estimates under non-standard conditions. In Proceedings of the Fifth Berkley Symposium on Mathematical Statistics and Probability Vol. 1, University of California Press: Berkley, CA, 1967: 221–233.

    Google Scholar 

  27. White H . Maximum likelihood estimation of misspecified models. Econometrica 1982; 50: 1–25.

    Article  Google Scholar 

  28. White H . A heteroskedasticity-consistent covariance matrix estimator and a direct test for heteroskedasticity. Econometrica 1980; 48: 817–830.

    Article  Google Scholar 

  29. Royall RM . Model robust confidence intervals using maximum likelihood estimators. Int Stat Rev 1986; 54: 221–226.

    Article  Google Scholar 

  30. StataCorp. Stata Statistical Software: Release 8 2003; Stata Corporation: College Station, TX.

  31. Clayton D, IBDREG. http://www-gene.cimr.cam.ac.uk/clayton/software/stata/README.txt, 2002.

Download references

Acknowledgements

The data analysed here were collected within the context of the Karonga Prevention Study (KPS), which has been supported by the British Leprosy Relief Association (LEPRA) and the Wellcome Trust, with contributions from the International Federation of Anti-Leprosy Organisations (ILEP) and the WHO/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases. We acknowledge the special contributions of Dr AC Crampin, and more than 50 field staff for the fieldwork, and the National Health Sciences Research Committee of Malawi for encouraging the KPS programme. We thank Dr Ruby Siddiqui for helpful comments. CW was supported by the British Medical Research Council.

Author information

Authors and Affiliations

  1. London School of Hygiene and Tropical Medicine, UK

    C Wallace & PEM Fine

  2. Barts and The London, Queen Mary's School of Medicine, UK

    C Wallace

  3. Wellcome Trust Centre for Human Genetics, Oxford, UK

    J Fitness, B Hennig & AVS Hill

  4. Victoria University of Wellington, New Zealand

    J Fitness

  5. Karonga Prevention Study, Malawi

    L Sichali, L Mwaungulu, JM Pönnighaus & DK Warndorff

  6. Cambridge Institute for Medical Research, UK

    D Clayton

Authors
  1. C Wallace
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Fitness
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B Hennig
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L Sichali
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L Mwaungulu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. JM Pönnighaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. DK Warndorff
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D Clayton
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. PEM Fine
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. AVS Hill
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C Wallace.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wallace, C., Fitness, J., Hennig, B. et al. Linkage analysis of susceptibility to leprosy type using an IBD regression method. Genes Immun 5, 221–225 (2004). https://doi.org/10.1038/sj.gene.6364062

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6364062

Keywords

This article is cited by

Search

Advanced search

Quick links