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American Journal of Epidemiology Vol. 136, No. 9: 1138-1147
Copyright © 1992 by The Johns Hopkins University School of Hygiene and Public Health

research-article

Familial Aggregation of a Disease Consequent upon Correlation between Relatives in a Risk Factor Measured on a Continuous Scale

John L. Hopper1, and John B. Carlin2

1Epidemiology Unit, Faculty of Medicine, University of Melbourne, Cartton Victoria, Australia
2Clinical Epidemiology and Biostatistics Unit, Royal Children's Hospital, Parkville Victoria, Australia

Reprint requests to Dr. John L Hopper, Epidemiology Unit, Faculty of Medicine, University of Melbourne, 151 Barry Street, Cartton, Victoria 3053, Australia.

Correlation between relatives in one or more risk factors for a disease will contribute to the risk in relatives of an affected individual, irrespective of the cause(s) of the correlation. In this paper, a model is proposed to quantify the relation between 1) the correlation ({rho}) between a random pair of relatives in a quantitative risk factor, 2) the dependence of the probability of being affected on a risk factor, assumed to be a logistic function and summarized by a risk ratio (RR) between upper and lower quartiles, and 3) the resultant disease association between relatives, represented as an odds ratio. For one risk factor, the odds ratio is almost independent of disease frequency across the range 0.001–0.1, and is approximately linearly related to {rho} on a logarithmic scale. An odds ratio between relatives of about 2 occurs if {rho} =1 and RR = 9, if {rho} = 0.6 and RR = 20, or if {rho} = 0.3 and RR = 100. For two independent risk factors with the same risk ratio and {rho}, the resultant odds ratio exceeds unity by about twice as much as when there is one risk factor. That is, even moderate familial aggregation of a disease is consistent with there being one or more strong familial (genetic and/or environmental) risk factors. Illustrations of the model are discussed. Am J Epidemiol 1992; 136: 1138–47

breast neoplasms; consanguinity; diet; family characteristics; genetics; risk factors


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