Can familial aggregation of disease be explained by familial aggregation of environmental risk factors?

Abstract

Although familial aggregation has been shown for many if not all diseases, it is often difficult to determine whether such aggregation is due to shared genes or shared environmental factors. The authors examine the effect of familial aggregation of environmental risk factors on familial aggregation of disease when there is no genetic susceptibility. An environmental risk factor with a relative risk (R) for disease and population exposure frequency (f) is assumed to be clustered among siblings with varying degrees of sibling correlation in exposure (c). The impact of varying R, f, and c is examined on two common measures of familial aggregation: the relative risk of disease for siblings of cases compared with siblings of controls, and the sibling recurrence risk. It can be shown that both measures increase with increasing R and c, but decrease at high levels of f. However, even in the face of complete correlation in exposure among siblings (c = 1), environmental risk factors that have values of R less than 10 lead to modest sibling relative risks (ranging from 1 to 2) and low recurrence risks. Similar findings are obtained when familial aggregation of two additive environmental factors is considered. Because many diseases show higher sibling relative risks and recurrence risks, this analysis suggests that simple familial clustering of environmental factors is unlikely to account entirely for familial aggregation of disease, and that genetic factors ought to play an important role in causing familial aggregation.