McDonnell Shannon K, Schaid Daniel J, Elbaz Alexis, Strain Kari J, Bower James H, Ahlskog J Eric, Maraganore Demetrius M, Rocca Walter A
Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Ann Neurol. 2006 May;59(5):788-95. doi: 10.1002/ana.20844.
To conduct complex segregation analyses of Parkinson's disease (PD).
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.
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 <or= 59 years) was an autosomal recessive model. The best fitting models for older onset PD (age > 59 years) were a recessive or an additive model.
The familial aggregation of PD may be explained in part by a major gene with additive effect on the penetrance.
对帕金森病（PD）进行复杂分离分析。
关于PD家族聚集性的数据仍存在争议。我们对明尼苏达州奥尔姆斯特德县具有代表性的162例PD患者的1234名亲属，以及梅奥诊所收治的411例PD患者的3009名亲属进行了一项历史性队列研究。通过直接或通过代理人对亲属进行访谈并筛查帕金森综合征，对筛查呈阳性的亲属进行检查，或获取其病历副本以确诊。对于居住在奥尔姆斯特德县的受试者，还从奥尔姆斯特德县历史学会档案和记录链接系统中获取了额外信息。
基于人群的先证者的32名亲属和转诊患者的69名亲属患上了PD（共101名）。将基于人群的样本和转诊样本相结合，总体上最能解释PD家族聚集性的模型是一个对 penetrance 有累加效应的主基因。该模型预测，假定的高危等位基因每增加一份，PD发病年龄平均降低约18岁。对于发病年龄较小的PD（年龄≤59岁），最佳拟合模型是常染色体隐性模型。对于发病年龄较大的PD（年龄>59岁），最佳拟合模型是隐性或累加模型。
PD的家族聚集性可能部分由一个对 penetrance 有累加效应的主基因来解释。
