Environmental Factors for Parkinson's in Swedish Twins

拟议研究的主要目的是评估 环境因素对帕金森病(PD)发病的重要性 以人口为基础的瑞典双胞胎样本。所有55岁及以上的双胞胎 瑞典双胞胎登记处目前正在接受计算机辅助 电话采访筛查最常见、最复杂的疾病，包括帕金森病， 痴呆症和抑郁症。我们已经对22,788人进行了筛查，并知道 有多少人的帕金森症状筛查呈阳性。在此基础上，我们预测 到2000年9月，将有2.6万人接受采访， 近1100人将筛查帕金森病阳性。医生会给你检查 所有潜在病例及其同卵双胞胎，以建立临床诊断。 所有入院病人的医疗纪录将会获得，以及 初级卫生保健设施。一旦看到足够的病例，临床 诊断结果将用于评估筛查的敏感性和特异性。 程序，并将调整识别阳性筛查的算法。 将采集血液样本以确认合子和 分子作用力。环境研究的主要方法论途径 因数将通过使用不和谐的配对来实现。会有 大约580对双胞胎，其中两人都还活着，对一个 正屏显示。有关环境暴露的信息将通过 由对诊断视而不见的第三方进行的计算机辅助调查。此外, 大多数双胞胎在28年前回答了一份关于接触的问卷 (职业、教育、居住史、健康状况、吸烟、饮食、 环境刺激物等)。配对的“同卵双生子”分析也是如此 由于数量遗传学方法将解决以下问题：1)在 帕金森氏不和谐双胞胎，有哪些环境风险因素 在受影响的双胞胎中促进疾病和/或保护未受影响的人 双胞胎？28年前报告的暴露有哪些长期影响？ 在疾病发作之前？在重要性上是否存在性别差异 这些暴露？2)是早先报告的遗传力低的报告 Tanner和他的同事确认老年男性-男性双胞胎为女性 而异性伴侣呢？3)遗传和共享的相对重要性 家族性环境对早发性帕金森病和迟发性帕金森病有何不同影响？ 对发病年龄的影响与对疾病易感性的影响是否不同？ 4)是否存在环境互作对基因分型的影响？在那里吗 候选基因和暴露之间的相互作用？5)在多大程度上 潜在共享性与非共享性对帕金森病的影响 环境影响，如痴呆症和抑郁症，这通常是并存的 和警察在一起？

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?