Fitness and the risk of illness and "spectrum disorder" in offspring, parents, and siblings.

Abstract

As shown by Essen-Moller [(1955).Acta Genet.5:334–342] and Risch [(1983).Behav. Genet.13:441–451], the effect of a disorder on fitness can substantially influence the risk of illness in relatives. This report expands on previous treatments by examining (1) the impact of fitness on the risk for illness and “spectrum disorder” in offspring, parents, and siblings as a function of the fitness of ill and spectrum individuals and (2) the effect on the risk of illness in relatives where fitness is related to the severity of illness. When fitness is the same for all affected individuals, decreasing fitness has little effect on the risk of spectrum or illness in offspring, diminishes rates of illness but increases rates of spectrum in parents, and diminishes rates of both illness and spectrum in siblings. When inversely correlated with severity of illness, fitness effects on risk of illness and spectrum in offspring can be nontrivial. Furthermore, as the fitness of the severe form of illness decreases, the risk in parents decreases for the severe form but increases for the mild form. For a trait with a substantial effect on fitness, misleading results may be produced by model fitting with risk data from relatives unless the pattern of fitness of spectrum, mildly affected, and severely affected individuals is taken into account.