Evidence for environmental causation of Parkinson's disease.

To address the question of whether Parkinson's disease (PD) is a genetic or an environmental disorder; (i) we modeled the hazard of PD using two-parameter hazard functions; and (ii) we investigated whether the hazard rate of index cases depended on the age of symptom onset in the affected parent (genetic model) or depended on the age of the index case at the time the affected parent developed PD (environmental model). We found that the hazard of PD increased monotonically with age according to a Weibull function. The risk associated with the presence of maternal PD did not depend on the age of onset of the affected mother but on the child's age at the time, the affected mother developed symptoms. The younger the child when the mother began to have symptoms, the higher the risk for the child. When the affected parent was the father, both models provided similar results. Whichever parent had PD, the age at onset of index cases correlated with their age at the time the affected parent developed PD, but not with the age of onset in the affected parent. Since the degree of environmental exposure shared by parents and children decreases as the child's age increases, these results indicate that PD is usually caused by an accumulation of transient environmental events. We provide evidence that this is not only true for sporadic cases but also for the majority of familial ones.