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The genetics literature is replete with results of candidate-gene association studies published mostly before the genome-wide association study (GWAS) became the new standard, but also continuing to this date. Their track record for replication is generally poor and discrepancies are typically attributed to differences in populations or environments. Are these results of any value, or should they be summarily discarded? Recent results from a GWAS for tuberculosis (TB) provide data that might put this question in perspective.1
TB is a serious health issue in the developing world, due to infection by Mycobacterium tuberculosis (MTB). Currently, about one third of the world's population is infected by MTB and 1/10 will develop active TB (http://www.who.int/tb/en/). Improved understanding of mechanisms of pathogenesis and host resistance is essential for improved control of TB. Human genetics is an indispensable tool for enhancing the understanding of the molecular basis of many common diseases. There is evidence that genetic factors may be involved in susceptibility to TB infection and activation of TB. This can be demonstrated by the fact of obvious ethnic differences. Blacks have about 1.5–2-fold greater risk than whites as shown by the tuberculin skin test,2 and concordance for TB is 2.5-fold higher among monozygotic than dizygotic …
Funding Funding for the project was provided by the Wellcome Trust under award 076113 and 085475.
Competing interests None.
Provenance and peer review Not commissioned; internally peer reviewed.
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