A likelihood approach to calculating risk support intervals.

Abstract

Genetic risks are usually computed under the assumption that genetic parameters, such as the recombination fraction, are known without error. Uncertainty in the estimates of these parameters must translate into uncertainty regarding the risk. To allow for uncertainties in parameter values, one may employ Bayesian techniques or, in a maximum-likelihood framework, construct a support interval (SI) for the risk. Here we have implemented the latter approach. The SI for the risk is based on the SIs of parameters involved in the pedigree likelihood. As an empirical example, the SI for the risk was calculated for probands who are members of chronic spinal muscular atrophy kindreds. In order to evaluate the accuracy of a risk in genetic counseling situations, we advocate that, in addition to a point estimate, an SI for the risk should be calculated.