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中国阿尔茨海默病的遗传学分析:成就与展望。

Genetic Analyses of Alzheimer's Disease in China: Achievements and Perspectives.

机构信息

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province , Kunming Institute of Zoology , Kunming , Yunnan 650223 , China.

Kunming College of Life Science , University of Chinese Academy of Sciences , Kunming , Yunnan 650204 , China.

出版信息

ACS Chem Neurosci. 2019 Feb 20;10(2):890-901. doi: 10.1021/acschemneuro.8b00435. Epub 2019 Feb 8.

Abstract

Since 2010, the Chinese have become one of the most aged populations in the world, leading to a severe burden of neurodegenerative disorders. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and has a high genetic heritability. In the past two decades, numerous genetic analyses, from linkage analyses and candidate gene studies to genome-wide association studies (GWASs) and next-generation sequencing studies, have identified dozens of AD susceptibility or causal genes. These studies have provided a comprehensive genetic view and contributed to the understanding of the pathological and molecular mechanisms of the disease. However, most of the recognized AD genetic risk factors have been reported in studies based on European populations or populations of European ancestry, and data about the genetics of AD from other populations has been very limited. As China has the largest AD population in the world and because of the remarkable genetic differences between the East and the West, deciphering the genetic basis and molecular mechanism in Chinese patients with AD may add key points to the full characterization of AD. In this review, we present an overview of the current state of AD genetic research in China, with an emphasis on genome-level studies. We also describe the challenges and opportunities for future advances, especially for in-depth collaborations, brain bank construction, and primate animal modeling. There is an urgent need to promote public awareness and increase our collaborations and data sharing.

摘要

自 2010 年以来,中国人成为世界上老龄化人口最多的国家之一,导致神经退行性疾病的负担严重。阿尔茨海默病(AD)是最常见的神经退行性疾病,具有很高的遗传率。在过去的二十年中,从连锁分析和候选基因研究到全基因组关联研究(GWAS)和下一代测序研究,已经鉴定出数十种 AD 易感性或因果基因。这些研究提供了全面的遗传视角,并有助于理解疾病的病理和分子机制。然而,大多数已识别的 AD 遗传风险因素都是在基于欧洲人群或欧洲血统人群的研究中报告的,而来自其他人群的 AD 遗传学数据非常有限。由于中国是世界上 AD 患者最多的国家,而且东西方之间存在显著的遗传差异,因此在中国 AD 患者中解析遗传基础和分子机制可能为 AD 的全面特征提供关键要点。在这篇综述中,我们概述了中国 AD 遗传研究的现状,重点介绍了基因组水平的研究。我们还描述了未来进展的挑战和机遇,特别是对于深入的合作、脑库建设和灵长类动物模型。迫切需要提高公众意识,增加我们的合作和数据共享。

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