对数百万人中罕见帕金森病变体的分析。
Analysis of rare Parkinson's disease variants in millions of people.
作者信息
Pitz Vanessa, Makarious Mary, Bandrés-Ciga Sara, Iwaki Hirotaka, Singleton Andrew, Nalls Mike, Heilbron Karl, Blauwendraat Cornelis
机构信息
NIA/NIH.
NIH.
出版信息
Res Sq. 2023 Apr 10:rs.3.rs-2743857. doi: 10.21203/rs.3.rs-2743857/v1.
OBJECTIVE
Although many rare variants have been reportedly associated with Parkinson's disease (PD), many have not been replicated or have failed to replicate. Here, we conduct a large-scale replication of rare PD variants.
METHODS
We assessed a total of 27,590 PD cases, 6,701 PD proxies, and 3,106,080 controls from three data sets: 23andMe, Inc., UK Biobank, and AMP-PD. Based on well-known PD genes, 834 variants of interest were selected from the ClinVar annotated 23andMe dataset. We performed a meta-analysis using summary statistics of all three studies.
RESULTS
The meta-analysis resulted in 11 significant variants after Bonferroni correction, including variants in and . At least 9 previously reported pathogenic or risk variants for PD did not pass Bonferroni correction in this analysis.
CONCLUSIONS
Here, we provide the largest rare variant meta-analysis to date, providing thorough information of variants confirmed, newly identified, or rebutted for their association with PD.
目的
尽管据报道许多罕见变异与帕金森病（PD）相关，但许多尚未得到重复验证或验证失败。在此，我们对罕见的PD变异进行大规模重复验证。
方法
我们评估了来自三个数据集的总共27590例PD病例、6701例PD替代者和3106080例对照：23andMe公司、英国生物银行和AMP-PD。基于知名的PD基因，从ClinVar注释的23andMe数据集中选择了834个感兴趣的变异。我们使用所有三项研究的汇总统计数据进行了荟萃分析。
结果
荟萃分析在进行Bonferroni校正后得出11个显著变异，包括 和 中的变异。在此分析中，至少9个先前报道的PD致病或风险变异未通过Bonferroni校正。
结论
在此，我们提供了迄今为止最大规模的罕见变异荟萃分析，提供了已确认、新发现或被反驳的与PD相关变异的详尽信息。
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