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American Journal of Epidemiology Vol. 155, No. 5 : 478-484
Copyright © 2002 by The Johns Hopkins University School of Hygiene and Public Health

ORIGINAL CONTRIBUTIONS

Sample Size Requirements for Association Studies of Gene-Gene Interaction

W. James Gauderman

From the Department of Preventive Medicine, School of Medicine, University of Southern California, 1540 Alcazar Street, Suite 220, Los Angeles, CA 90089 (e-mail: jimg{at}usc.edu).

In the study of complex diseases, it may be important to test hypotheses related to gene-gene (G x G) interaction. The success of such studies depends critically on obtaining adequate sample sizes. In this paper, the author investigates sample size requirements for studies of G x G interaction, focusing on four study designs: the matched-case-control design, the case-sibling design, the case-parent design, and the case-only design. All four designs provide an estimate of interaction on a multiplicative scale, which is used as a unifying theme in the comparison of sample size requirements. Across a variety of genetic models, the case-only and case-parent designs require fewer sampling units (cases and case-parent trios, respectively) than the case-control (pairs) or case-sibling (pairs) design. For example, the author describes an asthma study of two common recessive genes for which 270 matched case-control pairs would be required to detect a G x G interaction of moderate magnitude with 80% power. By comparison, the same study would require 319 case-sibling pairs but only 146 trios in the case-parent design or 116 cases in the case-only design. A software program that computes sample size for studies of G x G interaction and for studies of gene-environment (G x E) interaction is freely available (http://hydra.usc.edu/gxe).

association; case-control studies; genetics; interaction; research design; sample size

Abbreviations: G x G, gene-gene[interaction]; G x E, gene-environment[interaction]; GST, glutathione S-transferase


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