American Journal of Epidemiology Vol. 155, No. 11 : 1074-1079
Copyright © 2002 by The Johns Hopkins University School of Hygiene and Public Health
PRACTICE OF EPIDEMIOLOGY |
Investigation of Environmental and Host-related Risk Factors for Tuberculosis in Africa. II. Investigation of Host Genetic Factors
1 London School of Hygiene and Tropical Medicine, London, United Kingdom.
2 MRC Laboratories, Fajara, The Gambia.
3 Institut de Recherche pour le Développement, Dakar, Sénégal.
4 Programme National de Lutte Anti-Tuberculeuse, CHU Ignace Deen, Conakry, République de Guinée.
5 Projecto de Saude de Bandim, Danish Epidemiology Science Centre, Bissau, Guinea-Bissau.
6 National Leprosy/Tuberculosis Control Programme, Ministry of Health, Banjul, The Gambia.
7 Department of Internal Medicine, Faculty of Medicine, University of Florence, Florence, Italy.
8 Hopital Raoul Follereau, Bissau, Guinea-Bissau.
9 Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge, United Kingdom.
10 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
In an accompanying paper (Am J Epidemiol 2002;155:1066–73), the authors describe the design of a large multicenter study being carried out in three West African countries for investigation of the roles of environmental and host-related factors in the development of tuberculosis. In this paper, the authors review some evidence that host genetic factors play a role in susceptibility to tuberculosis. They describe the three components of the study that are designed to investigate the effect of host genetic factors on the development of tuberculosis: case-control and family-based association studies of candidate genes and analysis of affected relative pairs to screen the human genome for areas of linkage to the disease. The authors also address a number of methodological issues that arise, such as the effects of consanguinity, half-siblings, and nonpaternity. Lastly, they review opportunities to assess gene-environment interaction in the framework of the study, in light of current methodological knowledge. Consideration of these issues may be useful in the design of other studies of genetic susceptibility to infectious diseases, particularly those to be carried out in developing countries.
epidemiologic methods; genetics; infection; Mycobacterium tuberculosis; research design; risk factors; tuberculosis
Abbreviations: HLA, human leukocyte antigen
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