对阿尔茨海默病和帕金森病的全基因组关联研究进行分析，以确定这两种疾病是否具有共同的遗传风险。
Analysis of genome-wide association studies of Alzheimer disease and of Parkinson disease to determine if these 2 diseases share a common genetic risk.
出版信息
JAMA Neurol. 2013 Oct;70(10):1268-76. doi: 10.1001/jamaneurol.2013.448.
IMPORTANCE
Despite Alzheimer disease (AD) and Parkinson disease (PD) being clinically distinct entities, there is a possibility of a pathological overlap, with some genome-wide association (GWA) studies suggesting that the 2 diseases represent a biological continuum. The application of GWA studies to idiopathic forms of AD and PD have identified a number of loci that contain genetic variants that increase the risk of these disorders.
OBJECTIVE
To assess the genetic overlap between PD and AD by testing for the presence of potentially pleiotropic loci in 2 recent GWA studies of PD and AD.
DESIGN
Combined GWA analysis.
SETTING
Data sets from the United Kingdom, Germany, France, and the United States.
PARTICIPANTS
Thousands of patients with AD or PD and their controls.
MAIN OUTCOMES AND MEASURES
Meta-analysis of GWA studies of AD and PD.
METHODS
To identify evidence for potentially pleiotropic alleles that increased the risk for both PD and AD, we performed a combined PD-AD meta-analysis and compared the results with those obtained in the primary GWA studies.We also tested for a net effect of potentially polygenic alleles that were shared by both disorders by performing a polygenic score analysis. Finally, we also performed a gene-based association analysis that was aimed at detecting genes that harbor multiple disease-causing single-nucleotide polymorphisms, some of which confer a risk of PD and some a risk of AD.
RESULTS
Detailed interrogation of the single-nucleotide polymorphism, polygenic, and gene-based analyses resulted in no significant evidence that supported the presence of loci that increase the risk of both PD and AD.
CONCLUSIONS AND RELEVANCE
Our findings therefore imply that loci that increase the risk of both PD and AD are not widespread and that the pathological overlap could instead be “downstream” of the primary susceptibility genes that increase the risk of each disease.
重要性
尽管阿尔茨海默病（AD）和帕金森病（PD）在临床上是不同的实体，但它们可能存在病理重叠，一些全基因组关联（GWA）研究表明，这两种疾病代表了一个生物学连续体。将 GWA 研究应用于特发性 AD 和 PD 表明，有许多包含增加这些疾病风险的遗传变异的基因座。
目的
通过测试 2 项最近的 PD 和 AD GWA 研究中潜在多效性基因座的存在，评估 PD 和 AD 之间的遗传重叠。
设计
联合 GWA 分析。
设置
来自英国、德国、法国和美国的数据。
参与者
数千名 AD 或 PD 患者及其对照者。
主要结果和措施
AD 和 PD 的 GWA 研究的荟萃分析。
方法
为了确定增加 PD 和 AD 风险的潜在多效性等位基因的证据，我们进行了 PD-AD 联合荟萃分析，并将结果与主要 GWA 研究的结果进行了比较。我们还通过进行多基因评分分析来测试两种疾病共有的潜在多效性等位基因的净效应。最后，我们还进行了基于基因的关联分析，旨在检测携带多个致病单核苷酸多态性的基因，其中一些基因增加了 PD 的风险，而另一些则增加了 AD 的风险。
结果
对单核苷酸多态性、多基因和基于基因的分析的详细检查没有发现支持增加 PD 和 AD 风险的基因座存在的显著证据。
结论和相关性
因此，我们的研究结果表明，增加 PD 和 AD 风险的基因座并不广泛，而病理重叠可能是增加每种疾病风险的主要易感基因的“下游”。
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