The genetic architecture of Parkinson's disease.
The genetic architecture of Parkinson's disease.
复制标题
帕金森氏病的遗传结构。
DOI：
10.1016/s1474-4422(19)30287-x
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发表时间：
2020-02
期刊：
影响因子：
--
通讯作者：
Singleton AB
中科院分区：
文献类型：
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作者：
Blauwendraat C;Nalls MA;Singleton AB
帕金森病是一种复杂的神经退行性疾病，罕见和常见的遗传变异都有助于疾病的风险，发病和进展。超过20个基因的突变与该疾病有关，其中大多数是高度外显的，通常会导致早发或非典型症状。虽然我们对帕金森病遗传基础的理解已经有了很大的进步，但还有很多工作要做。进一步的疾病相关的常见遗传变异性仍有待确定，确定罕见风险等位基因的工作才刚刚开始。迄今为止，全基因组关联研究已经确定了90个独立的风险相关变异。然而，其中大多数已经在欧洲血统的患者中发现，我们对其他人群中帕金森病的遗传学知之甚少。我们对已确定的风险等位基因的生物学功能的理解有限，尽管帕金森病风险变体似乎与已知的帕金森病基因和溶酶体相关基因非常接近。在过去的十年中，人们已经做出了多种努力来研究帕金森病的遗传结构，机器学习、单细胞RNA测序和高通量筛选等新兴技术将提高我们对遗传风险的理解。
Parkinson’s disease is a complex neurodegenerative disorder for which both rare and common genetic variants contribute to disease risk, onset, and progression. Mutations in more than 20 genes have been associated with the disease, most of which are highly penetrant and often cause early onset or atypical symptoms. Although our understanding of the genetic basis of Parkinson’s disease has advanced considerably, much remains to be done. Further disease-related common genetic variability remains to be identified and the work in identifying rare risk alleles has only just begun. To date, genome-wide association studies have identified 90 independent risk-associated variants. However, most of them have been identified in patients of European ancestry and we know relatively little of the genetics of Parkinson’s disease in other populations. We have a limited understanding of the biological functions of the risk alleles that have been identified, although Parkinson’s disease risk variants appear to be in close proximity to known Parkinson’s disease genes and lysosomal-related genes. In the past decade, multiple efforts have been made to investigate the genetic architecture of Parkinson’s disease, and emerging technologies, such as machine learning, single-cell RNA sequencing, and high-throughput screens, will improve our understanding of genetic risk.