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American Journal of Epidemiology Vol. 133, No. 3: 246-256
Copyright © 1991 by The Johns Hopkins University School of Hygiene and Public Health

research-article

Case-Control Studies of Environmental Influences in Diseases with Genetic Determinants, with an Application to Alzheimer's Disease

John C. S. Breitner1,, Edmond A. Murphy2 and Max A. Woodbury3

1Department of Psychiatry, and Center for the Study of Aging, Duke University Medical Center Durham, NC
2Department of Medical Genetics, the Johns Hopkins University School of Medicine Baltimore, MD
3Department for the Study of Aging, and Center for Demographic Studies, Duke University Durham, NC

Reprint requests to Dr. John C S. Breitner, Department of Psychiatry, Box 3925, Duke University Medical Center, Durham, NC 27710

Many diseases have both genetic and environmental determinants. Some require both, and the disease phenotype then appears only when a vulnerable genotype is expressed after interaction with environmental factors. The detection of such environmental factors has received little prior consideration in diseases with genetic causes. In particular, case-contsol studies of such diseases may compare exposures among cases, who have the susceptible genotype, and controls who mostly lack it. The authors explored the likely results of such studies, using the example of Alzheimer's disease as an illness where environmental factors may interact with a necessary susceptible genotype to accelerate disease expression. They found that case-control studies of environmental factors in complex genetic diseases will usually produce an odds ratio that differs little from the relative risk among susceptible individuals. In rare situations, however, the discrepancy may be gross. The statistical power of such studies also agrees well with familiar published estimates, suggesting that little power is lost even though the controls are mostly not susceptible. Power may be increased, however, in studies of common illnesses with genetic determinants when the case-control method is applied among discordant monozygotic twins.

Alzheimer's disease; case-control studies; genetics, medical; risk; risk factors


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