Complex segregation analysis of Parkinson's disease: The Mayo Clinic family study
Complex segregation analysis of Parkinson's disease: The Mayo Clinic family study
复制标题
DOI：
10.1002/ana.20844
复制
发表时间：
2006-05-01
影响因子：
11.2
通讯作者：
Rocca, WA
中科院分区：
文献类型：
--
作者：
McDonnell, SK;Schaid, DJ;Rocca, WA
目的：对帕金森病（PD）进行复杂分离分析。我们对明尼苏达州奥姆斯特德县162例PD患者的1,234名亲属和马约诊所411例PD患者的3,009名亲属进行了一项历史队列研究。直接或通过代理人对亲属进行访谈和帕金森症筛查，对筛查阳性的人进行检查，或获得他们的医疗记录副本以确认诊断。居住在奥姆斯特德县的受试者，额外的信息从奥姆斯特德县历史学会的档案，并从一个records-linkage system.Results：32个亲属的人口为基础的先证者和69个亲属的转诊患者发展PD（共101）。结合基于人群的样本和转诊样本，最能解释PD整体家族聚集性的模型是一个对外显率具有加性效应的主基因。该模型预测，对于推定的高风险等位基因的每个拷贝，PD发作时的年龄平均降低约18岁。对于较年轻发病的PD（年龄59岁），最佳拟合模型是隐性或加性模型。解释：PD的家族聚集性可以部分地由主基因对遗传率具有加性效应来解释。
Objective: To conduct complex segregation analyses of Parkinson's disease (PD).Methods: Data on the familial aggregation of PD remain conflicting. We conducted a historical cohort study of 1,234 relatives of 162 patients with PD representative of people of Olmsted County, MN, and of 3,009 relatives of 411 patients with PD referred to the Mayo Clinic. Relatives were interviewed and screened for parkinsonism either directly or through a proxy, those who screened positive were examined, or a copy of their medical record was obtained to confirm the diagnosis. For subjects who resided in Olmsted County, additional information was obtained from the archives of the Olmsted County Historical Society and from a records-linkage system.Results: Thirty-two relatives of population-based probands and 69 relatives of referral patients developed PD (101 in total). Combining population-based and referral samples, the model that best explained the familial clustering of PD overall was a major gene with additive effect on the penetrance. This model predicted an average decrease in age at onset of PD of approximately 18 years for each copy of the putative high-risk allele. The best fitting model for younger onset PD (age 59 years) were a recessive or an additive model.Interpretation: The familial aggregation of PD may be explained in part by a major gene with additive effect on the penetrance.