Genetic epidemiology of Parkinson's disease.

The cause of Parkinson's disease (PD) is unknown. The major risk factors identified to date are family history, age, and elements of rural living. Nearly one-third of all PD cases are familial, a small subset of which appears autosomal dominant; however, the majority exhibit no clear inheritance pattern. Autosomal dominant PD is genetically heterogeneous: two PD genes have been mapped to chromosomes 2 and 4 and there may be additional as yet unidentified genes. The common forms of PD-both familial and sporadic cases-appear to involve a complex interplay of genetic susceptibility and environmental exposure. The observations that rural residence and pesticide exposure increase the risk of developing PD, and that a synthetic drug, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, can cause parkinsonism, suggest that at least a subset of PD may be caused by a toxin. Furthermore, modest but significant associations have been reported between PD susceptibility and genes that regulate metabolism of drugs and neurotoxins. There is also evidence for mitochondrial dysfunction in PD, a finding that was recently traced to anomalies in mitochondrial DNA. At the present time, the genetics of PD appear to be complex, involving multiple nuclear genes and possibly mitochondrial genes as well.