Estimating the relative recurrence risk ratio using a global cross‐ratio model

Abstract

The relative recurrence risk ratio λ_R (and particularly the sibling recurrence risk ratio, λ_S ) is often of interest to those wanting to quantify the genetic contribution towards risk of disease or to discriminate between different genetic models. However, estimating λ_R for complex diseases for which genetic and environmental risk factors are both involved is not straightforward. Ignoring environmental factors may lead to inflated estimates of λ_R. We present a marginal model which uses a copula function to model the association in cumulative incidence rates between pairs of relatives. This model is applicable to present‐state data and allows estimation of risk of disease in a pair of relatives (and hence λ_R), given measured environmental covariates. We apply the model to leprosy among sibling pairs from the Karonga district, Malawi. If risk factors are ignored, the apparent λ_S in this population is over 3. Accounting for known nongenetic risk factors reduces it to just under 2. Genet Epidemiol 25:293–302, 2003.