Am. J. Respir. Crit. Care Med., Volume 162, Number 6, December 2000, 2188-2193

Evidence for Genetic Associations between Asthma, Atopy, and Bronchial Hyperresponsiveness
A Study of 8- to 18-Yr-Old Twins

JANE R. CLARKE, MARK A. JENKINS, JOHN L. HOPPER, JOHN B. CARLIN, CAROL MAYNE, DAVID G. CLAYTON, MARITA F. DALTON, DIANE P. HOLST, and COLIN F. ROBERTSON

Respiratory & Cystic Fibrosis Unit, The Birmingham Children's Hospital NHS Trust, Birmingham, United Kingdom; Centre for Genetic Epidemiology, The University of Melbourne, Carlton, Victoria, Australia; Clinical Epidemiology & Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Victoria, Australia; Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Queensland, Australia; Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge, United Kingdom; and Department of Respiratory Medicine, Royal Children's Hospital, Parkville, Victoria, Australia

We measured asthma in the last 12 mo, diagnosed by a respiratory physician at interview; atopy, defined by a positive skin prick test to any of eight common allergens; and bronchial hyperresponsiveness (BHR) to hypertonic saline, in 381 twin pairs aged 8 to 18 yr selected from the Australian Twin Registry183 monozygous (MZ) and 198 dizygous (DZ). The associations between twins, as measured by an odds ratio, were greater in MZ pairs compared with DZ pairs for asthma: 25.6 (95% confidence interval 11.3- 57.8) versus 1.9 (1.0-3.5); atopy: 14.6 (7.1-30.1) versus 2.5 (1.4- 4.5); and BHR: 14.1 (6.4-31.0) versus 4.2 (2.1-8.6) (all p < 0.002). The associations between each pair of traits within an individual were slightly greater than the association between one trait in a twin and the other trait in the cotwin (cross-trait cross-pair) in MZ pairs. Further, the associations in MZ pairs were greater than in DZ pairs (p < 0.05). Under the assumptions of the classic twin model, these data suggest that the strong cross-sectional associations between these three traits are due to an overlap between the genetic factors involved in each of these three traits.

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