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基因组测序分析鉴定出与路易体痴呆相关的新基因座，并深入了解其遗传结构。

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture.

机构信息

Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.

Neurodegenerative Diseases Research Unit, Laboratory of Neurogenetics, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.

出版信息

Nat Genet. 2021 Mar;53(3):294-303. doi: 10.1038/s41588-021-00785-3. Epub 2021 Feb 15.

DOI:10.1038/s41588-021-00785-3
PMID:33589841
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7946812/
Abstract

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.

摘要

路易体痴呆（LBD）的遗传基础尚不清楚。在这里，我们对大量的 LBD 病例和神经科健康对照者进行了全基因组测序，以研究这种研究较少的痴呆形式的遗传结构，并为科学界提供资源。全基因组关联分析确定了五个独立的风险位点，而全基因组基因聚集测试则提示 GBA 基因的突变。遗传风险评分表明，LBD 与阿尔茨海默病和帕金森病具有风险特征和途径，这为理解这种与年龄相关的神经退行性疾病的复杂遗传结构提供了更深入的分子认识。

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