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Heredity versus Environment in Tuberculosis in Twins

The 1950s United Kingdom Prophit Survey—Simonds and Comstock Revisited

¹ Department of Infectious Diseases and ² Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

Correspondence and requests for reprints should be addressed to Jaap T. van Dissel, M.D., Ph.D., Department of Infectious Diseases, C5-P, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: j.t.van_dissel{at}lumc.nl

Rationale: In his 1978 article on tuberculosis (TB) in twins, Comstock concluded that the 2.5-fold higher concordance rate for TB among monozygotic versus dizygotic twins in the Prophit survey of the 1950s implicated inherited susceptibility as a major risk factor for TB in humans. His analysis did not take into account strong imbalance of variables within subgroups, underestimating possible confounding effects of environmental factors.

Objectives: To reconsider the role of environmental versus hereditary factors in determining the concordance rate of TB among twin pairs.

Methods: Reanalysis of the Prophit Survey.

Measurements and Main Results: A known Mycobacterium tuberculosis–positive or M. tuberculosis–negative sputum in the index TB case markedly influenced the odds ratio (OR) of concordance in the twin pairs. In 87 pairs with co-twins exposed to a sputum-negative index case, monozygotic and dizygotic twins did not differ in concordance for TB (OR, 1.1; 95% confidence interval [95% CI], 0.4–2.8). A higher concordance rate for TB among monozygotic versus dizygotic twins was confined to 106 pairs with the co-twins exposed to a sputum-positive index case (OR, 3.4; 95% CI, 1.6–7.2), and was highest in adolescent twins living together. ORs of TB concordance were proportional to intensity of exposure (sputum smear positivity, physical proximity between twin pairs, contagiousness of disease, and living together) rather than to zygosity.

Conclusions: In the Prophit survey of susceptibility to TB among twins, environmental factors (i.e., intensity of exposure to tubercle bacilli) outweigh the importance of hereditary factors. Environmental factors and the context of transmission should be given more emphasis when studying interindividual and population differences in susceptibility to infectious diseases such as TB.

Key Words: tuberculosis • human genetics • heredity • twins

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject The relative contributions of environmental versus genetic factors in the development of tuberculosis have not been completely delineated. What This Study Adds to the Field This analysis of twin studies in tuberculosis suggests that environmental rather than hereditary factors largely determine the concordance rate of disease in twins.

 

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Of Contagion and Inherited Susceptibility: An Epidemiologic Tribute to George W. Comstock

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