Epistatic modeling in rheumatoid arthritis: an application of the Risch theory

Rheumatoid arthritis (RA) is a disease of unknown etiology but with a presumed complex pattern of inheritance. Risch [Am J Hum Genet 46:222-228, 1990] has shown that the recurrence risk ratio, lambda R, (which is defined as the risk to type R relatives vs. the population prevalence) can be used to evaluate patterns of inheritance in genetically complex diseases. We have used the Risch theory to examine some multiple locus models of inheritance in RA. Recurrence risk ratios in MZ twins and in 1st, 2nd, and 3rd degree relatives are summarized from the literature. The limited data available supports at least a two-locus model of inheritance for RA (assuming that one locus is HLA). Better estimates of the recurrence risk ratios in RA families are required so that the Risch theory can be pursued further.