Twin studies and the genetics of Parkinson's disease--a reappraisal.

Parkinson's disease (PD) has long been regarded as having a hereditary component. However, three recent twin studies have been interpreted as excluding any significant genetic component in the etiology of PD. In this article, we reexamine these twin studies and argue that such a conclusion is premature. We review statistical tests of twin concordance rates, including calculation of G, the coefficient of genetic determination. When variation in a trait is due entirely to genetic factors G = 1, and when variation in a trait is due entirely to nongenetic factors G = 0. We conclude that: (a) low monozygotic concordance rates can be compatible with substantial genetic contribution to etiology; (b) the PD twin study data give substantial optimal values of G (up to 0.78) but the very broad 95% confidence limits for G make it impossible for the twin study data to prove or disprove a substantial genetic component to the etiology of PD; and (c) changing clinical concepts of PD have undermined the assumptions underlying the methodology of the PD twin studies. We review three genetic models that are biologically plausible for PD and are compatible with the low twin concordance rates. Finally, we suggest that further family studies, including linkage studies, are needed to resolve this question.