Genomic mechanisms in Alzheimer's disease
Genomic mechanisms in Alzheimer's disease
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DOI：
10.1111/bpa.12882
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发表时间：
2020-09-01
期刊：
影响因子：
6.4
通讯作者：
Tanzi, Rudolph E.
中科院分区：
文献类型：
--
作者：
Bertram, Lars;Tanzi, Rudolph E.
阿尔茨海默氏病（AD）是最常见的神经退行性疾病，并且由于其患病率不断增加，已成为老龄化人口中主要的公共卫生问题之一。 AD 发病和进展的分子原因是多方面的，迄今为止仍不完全清楚。近四十年的研究已经清楚地表明，遗传学在 AD 易感性中发挥着至关重要的作用，可能与非遗传因素相结合。由于高通量基因组学技术在规模不断增大的数据集中的出现和应用，该领域在过去 10 年中获得了相当大的发展势头和新颖的见解。在阿尔茨海默病分子病因学小型研讨会的这篇文章中，我们回顾了阿尔茨海默病基因组学研究的现状。为此，我们仔细研究并讨论了该领域两个最大、最新的全基因组关联研究（GWAS）的主要发现，即Jansenet al（Nat Genet 51：404-413）和Kunkleet al（Nat Genet 51：414-430）发表的论文。特别关注的是两项研究中重叠的基因组学发现，以及它们在提高我们对这种毁灭性疾病背后的“基因组机制”的理解方面提供的新见解。
Alzheimer's disease (AD) is the most common neurodegenerative disease and, owing to its increasing prevalence, represents one of the leading public health problems in aging populations. The molecular causes underlying the onset and progression of AD are manifold and hitherto still incompletely understood. Research over nearly four decades has clearly delineated genetics to play a crucial role in AD susceptibility, likely in concert with non-genetic factors. The field has gained considerable momentum and novel insights over the past 10 years owing to the advent and application of high-throughput genomics technologies in datasets of increasing size. In this contribution to the Mini-Symposium on the Molecular Etiology of Alzheimer's Disease, we review the current status of genomics research in AD. To this end, we scrutinize and discuss the main findings from the two largest and most current genome-wide association studies (GWAS) in the field, that is, the papers published by Jansenet al(Nat Genet 51:404-413) and Kunkleet al(Nat Genet 51:414-430). Particular focus is laid on genomics findings overlapping across both studies and on the novel insights they provide in terms of improving our understanding of the "genomic mechanisms" underlying this devastating disease.