On the measurement of susceptibility to genetic factors

Geneticists usually measure the phenotypic effects of a single gene trait in terms of penetrance and recurrence risks in relatives of affected individuals, while epidemiologists usually compute measures of relative and attributable risks. These concepts can be merged to measure the proportion of individuals "susceptible" to a genetic factor. In the context of a sufficient cause model, susceptibility can be defined as the underlying factor(s) sufficient to make a person develop disease because of the genetic factor in the absence of other causes. The proportion of susceptibles to the genetic factor in the population differs conceptually and often arithmetically from the penetrance of the genotype especially for common diseases with etiologic heterogeneity. For a wide range of disease and allele frequencies, it can be shown that the proportion of susceptibles can be approximated by the risk difference measure (i.e., difference between penetrance with the genotype and penetrance without the genotype). We also apply the concept of susceptibility to estimate familial recurrence of disease due to a genetic factor. This measure of familial recurrence differs conceptually from simple recurrence risk and can be approximated by the familial risk difference measure (i.e., difference between recurrence risks in relatives of cases and relatives of controls) for a wide range of disease and allele frequencies.