The primary purpose of the proposed research is to assess the importance of environmental factors for Parkinson's Disease (PD) in a population-based sample of Swedish Twins. All twins 55 years of age and older in the Swedish Twin Registry are currently undergoing computer assisted telephone interviews to screen for most common, complex diseases, including PD, dementia, and depression. We have already screened 22,788 individuals and know how many screen positive for Parkinson's symptoms. On this basis we project that, from the 26,000 individuals who will be interviewed by September 2000, nearly 1100 individuals will screen positive for PD. A physician will examine all potential cases and their co-twins for establishing clinical diagnosis. Medical records will be obtained for all hospital admissions as well as from primary health care facilities. Once sufficient cases have been seen, clinical diagnoses will be used to evaluate sensitivity and specificity of the screening procedure, and algorithms for identifying positive screens will be adjusted. Blood samples will be obtained for purposes of zygosity confirmation and molecular work. The main methodological approach to studying environmental factors will be through the use of discordant pairs. There will be approximately 580 twin pairs, in which both are alive, discordant for a positive screen. Information about environmental exposures will be secured with a computer assisted survey by a third party blind to diagnosis. In addition, most twins responded 28 years ago to a questionnaire concerning exposures (occupation, education, residential history, health status, smoking, diet, environmental irritants, etc.). Matched-pair """"""""co-twin control"""""""" analyses as well as quantitative genetic approaches will address the following questions: 1) In PD discordant twin pairs, what are the environmental risk factors that contribute to the disease in the affected twin and or protect the unaffected twin? What are the long-term influences of exposures reported 28 years ago and prior to onset of the disease? Are there sex differences in the importance of these exposures? 2) Are earlier reports of low heritability reported for elderly male-male twins by Tanner and colleagues confirmed for female-female and unlike-sexed pairs? 3) Is the relative importance of genetic and shared familial environmental influences different for early than for late onset PD? Are influences on age at onset different than those for liability to disease? 4) Are there indications of genotype by environment interaction? Are there interactions between candidate genes and exposures? 5) To what extent is liability to PD influenced by the same latent shared and non-shared environmental influences as dementia and depression, which are often co-morbid with PD?
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