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阿尔茨海默病、肌萎缩侧索硬化症、路易体痴呆和帕金森病之间的遗传重叠。

The genetic overlap between Alzheimer's disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson's disease.

机构信息

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, the Netherlands.

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, the Netherlands.

出版信息

Neurobiol Aging. 2023 Jul;127:99-112. doi: 10.1016/j.neurobiolaging.2023.03.004. Epub 2023 Mar 12.

Abstract

Neurodegenerative diseases are a group of disorders characterized by neuronal cell death causing a variety of physical and mental problems. While these disorders can be characterized by their phenotypic presentation within the nervous system, their aetiologies differ to varying degrees. The majority of previous genetic evidence for overlap between neurodegenerative diseases has been pairwise. In this study, we aimed to identify overlap between the 4 investigated neurodegenerative disorders (Alzheimer's disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson's disease) at the variant, gene, genomic locus, gene-set, cell, or tissue level, with specific interest in overlap between 3 or more diseases. Using local genetic correlation, we found 2 loci (TMEM175 and HLA) that were shared across 3 disorders. We also highlighted genes, genomic loci, gene sets, cell types, and tissue types which may be important to 2 or more disorders by analyzing the association of variants with a common factor estimated from the 4 disorders. Our study successfully highlighted genetic loci and tissues associated with 2 or more neurodegenerative diseases.

摘要

神经退行性疾病是一组以神经元细胞死亡为特征的疾病,可导致多种身心问题。虽然这些疾病可以根据其在神经系统中的表型表现来进行特征描述,但它们的病因在不同程度上存在差异。以前大多数神经退行性疾病重叠的遗传证据都是两两之间的。在这项研究中,我们旨在确定 4 种研究中的神经退行性疾病(阿尔茨海默病、肌萎缩侧索硬化症、路易体痴呆和帕金森病)在变异、基因、基因组位置、基因集、细胞或组织水平上的重叠,特别关注 3 种或更多疾病之间的重叠。使用局部遗传相关性,我们发现了 2 个跨越 3 种疾病的位点(TMEM175 和 HLA)。我们还通过分析与从 4 种疾病中估计的共同因子相关的变异,突出了与 2 种或更多疾病相关的基因、基因组位置、基因集、细胞类型和组织类型。我们的研究成功地突出了与 2 种或更多神经退行性疾病相关的遗传位置和组织。

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