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American Journal of Epidemiology Vol. 140, No. 5: 453-460
Copyright © 1994 by The Johns Hopkins University School of Hygiene and Public Health

research-article

An Investigation of Gene-Environment Interaction in the Etiology of Rheumatoid Arthritis

Paul Brennan and Alan J. Silman

From the Arthritis and Rheumatism Council Epidemiology Research Unit, University of Manchester Manchester, England

Reprint requests to Paul Brennan, ARC Epidemiology Research Unit, Stopford Building, University of Manchester. Oxford Rd., Manchester M13 9PT, England

The etiology of rheumatoid arthntis is explained by both genetic arid hormonal environment factors. Using a survey of twins conducted in the British Isles in 1989, the authors have investigated the extent of a possible genetic-hormonal environment interaction in conferring susceptibility for rheumatoid arthritis. This was done by comparing the hormonal history of three groups of cases and controls: 1) disease-discordant monozygotic twins, thus matching cases and controls for genetic susceptibility; 2) disease-discordant dizygotic twins; and 3) a group of twins with rheumatoid arthritis who were age matched to population controls. When the medical histories of twins with rheumatoid arthritis were compared with those of population controls, both breast feeding and infertility problems appeared to be risk factors for the disease (odds ratios = 2.01 and 4.09, respectively). Also, oral contraceptive use appeared to have a protective effect (odds ratio = 0.43). However, when both monozygotic and dizygotic twins were compared, these effects were either less apparent or nonexistent. Our results therefore suggest that there does not exist any evidence of strong interaction between genetic and hormonal environment factors. More notably, in the absence of such an interaction, the comparison of both monozygotic and dizygotic discordant twins was overmatched and therefore of tow power. The extent of any overmatching was measured using the kappa statistic.

arthritis; rheumatoid; case-control studies; environment; genetics; twins


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