Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montréal, Quebec, Canada.
Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and neurosurgery, McGill University, Montréal, Quebec, Canada.
Neurobiol Aging. 2021 Apr;100:119.e7-119.e13. doi: 10.1016/j.neurobiolaging.2020.10.019. Epub 2020 Oct 31.
Rare mutations in genes originally discovered in multigenerational families have been associated with increased risk of Parkinson's disease (PD). The involvement of rare variants in DNAJC13, UCHL1, HTRA2, GIGYF2, and EIF4G1 loci has been poorly studied or has produced conflicting results across cohorts. However, they are still being often referred to as "PD genes" and used in different models. To further elucidate the role of these 5 genes in PD, we fully sequenced them using molecular inversion probes in 2408 patients with PD and 3444 controls from 3 different cohorts. A total of 788 rare variants were identified across the 5 genes and 3 cohorts. Burden analyses and optimized sequence Kernel association tests revealed no significant association between any of the genes and PD after correction for multiple comparisons. Our results do not support an association of the 5 tested genes with PD. Combined with previous studies, it is unlikely that any of these genes plays an important role in PD. Their designation as "PARK" genes should be reconsidered.
最初在多代家族中发现的基因中的罕见突变与帕金森病 (PD) 的风险增加有关。DNAJC13、UCHL1、HTRA2、GIGYF2 和 EIF4G1 基因座中的罕见变异的参与在不同的队列中研究得很少或产生了相互矛盾的结果。然而，它们仍然经常被称为“PD 基因”，并在不同的模型中使用。为了进一步阐明这 5 个基因在 PD 中的作用，我们使用分子反转探针在来自 3 个不同队列的 2408 名 PD 患者和 3444 名对照中对它们进行了全序列分析。在 5 个基因和 3 个队列中总共鉴定出了 788 个罕见变体。在进行多次比较的校正后，负担分析和优化序列核关联测试显示，这些基因中的任何一个与 PD 之间均无显著关联。我们的结果不支持 5 个测试基因与 PD 之间存在关联。结合以前的研究，这些基因中没有任何一个很可能在 PD 中起重要作用。应重新考虑将它们指定为“PARK”基因。
