Epidemiology versus genetics in Parkinson's disease: progress in resolving an age-old debate.

Determining the relative contributions of environment and heredity to the cause of Parkinson's disease (PD) is more than an academic issue because its resolution dictates future research directions to an enormous degree. This article reviews new advances on both sides of this equation. The recent identification of the genetic mutation responsible for parkinsonism in a large Italian kindred is likely to provide exciting new research opportunities but the mutation does not appear to be responsible for the vast majority of PD. A large twin study also points away from genetic influences as important, at least in patients with disease beginning after the age of 50 years. On the other hand, genetic influences loom large in younger-onset disease. With regard to the environment, epidemiologic studies have provided only broad, thought-tantalizing clues to the cause of the disease. Although rural living, well-water consumption, and exposure to pesticides have emerged as potential risk factors, identification of specific agents is lacking, and aging remains as the only unequivocal risk factor for the disease. The surprisingly strong inverse relationship between cigarette smoking and PD provides an intriguing lead, but novel experimental avenues to pursue this observation are not readily obvious. The amyotrophic lateral sclerosis/dementia/parkinsonism complex in the western Pacific suggests the possibility of long-latency toxins, but pinning down a specific causative agent for this syndrome has eluded investigators to date. Despite the many obstacles ahead, however, research on PD appears to be more robust than ever, and our quest to find its cause appears to be under a full head of steam as we approach the 21st century.