Predicting recurrence risks under epistatic models

Abstract

We present the expected recurrence risks to a sib of an affected proband under 4 simple 2-locus epistatic models for various allele frequencies at both the disease locus and the epistatic locus. Four obvious epistatic models are considered: an autosomal recessive disease with both 1) dominant and 2) recessive masking by the epistatic locus, and an autosomal dominant disease again with both 3) dominant and 4) recessive masking. Expected recurrence risks to a sib of an affected proband and to a sib of an affected proband with another normal sib are presented in the absence of information on parental status. Similar risks are presented for the case where both parents are known to be phenotypically normal. These recurrence risks were calculated using a convenient matrix notation which allows sequential calculation of genotypic probabilities. In general, 2-locus epistatic models can give surprisingly low recurrence risks, and often these risks, especially for models of recessive diseases, fall into the range associated with a more general multifactorial model for liability.