Genetic susceptibility to Parkinson's disease.

Genetic factors clearly cause Lewy-body Parkinson's disease (PD) in a subset of autosomal-dominant families. However, most cases of PD are sporadic. The two most likely models of four discussed for sporadic PD are the reduced penetrance model and the multifactorial model. Sporadic PD is likely to be caused by the combined effect of environmental precipitating factors and genetic susceptibility factors. Because the number of major genetic factors is likely to be small, these hypotheses can be tested and genetic factors located using linkage mapping techniques. The affected pair analysis methods are especially suited to PD. Finding the genetic susceptibility factors for PD is important because this may be the fastest way to identify the environmental precipitating factors and because it may lead to prevention of PD. Because of the usefulness of identifying genetic susceptibility factors for PD, we are carrying out linkage studies in a group of 16 large autosomal-dominant families with PD and more than 300 living affected PD pairs.