Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture
(2021) In Nature Genetics 53(3). p.294-303- 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. © 2021, This is a U.S. government... (More)
- 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. © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/e50a830b-0525-4906-8ecc-a0f0ce39a5f9
- author
- Chia, Ruth ; Londos, Elisabet LU and Scholz, S.W.
- author collaboration
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer disease, Article, diffuse Lewy body disease, gene locus, gene mutation, gene sequence, genetic risk score, genetic susceptibility, genome analysis, genome-wide association study, human, Parkinson disease, priority journal, whole genome sequencing, case control study, clinical trial, gene expression profiling, genetic predisposition, genetics, human genome, multicenter study, single nucleotide polymorphism, alpha synuclein, BIN1 protein, human, GBA protein, human, glucosylceramidase, nuclear protein, signal transducing adaptor protein, SNCA protein, human, tumor suppressor protein, Adaptor Proteins, Signal Transducing, alpha-Synuclein, Alzheimer Disease, Case-Control Studies, Gene Expression Profiling, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Glucosylceramidase, Humans, Lewy Body Disease, Nuclear Proteins, Parkinson Disease, Polymorphism, Single Nucleotide, Tumor Suppressor Proteins
- in
- Nature Genetics
- volume
- 53
- issue
- 3
- pages
- 10 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85101937262
- pmid:33589841
- ISSN
- 1546-1718
- DOI
- 10.1038/s41588-021-00785-3
- language
- English
- LU publication?
- yes
- id
- e50a830b-0525-4906-8ecc-a0f0ce39a5f9
- date added to LUP
- 2021-12-28 14:10:03
- date last changed
- 2022-05-13 01:05:28
@article{e50a830b-0525-4906-8ecc-a0f0ce39a5f9,
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. © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.}},
author = {{Chia, Ruth and Londos, Elisabet and Scholz, S.W.}},
issn = {{1546-1718}},
keywords = {{Alzheimer disease; Article; diffuse Lewy body disease; gene locus; gene mutation; gene sequence; genetic risk score; genetic susceptibility; genome analysis; genome-wide association study; human; Parkinson disease; priority journal; whole genome sequencing; case control study; clinical trial; gene expression profiling; genetic predisposition; genetics; human genome; multicenter study; single nucleotide polymorphism; alpha synuclein; BIN1 protein, human; GBA protein, human; glucosylceramidase; nuclear protein; signal transducing adaptor protein; SNCA protein, human; tumor suppressor protein; Adaptor Proteins, Signal Transducing; alpha-Synuclein; Alzheimer Disease; Case-Control Studies; Gene Expression Profiling; Genetic Predisposition to Disease; Genome, Human; Genome-Wide Association Study; Glucosylceramidase; Humans; Lewy Body Disease; Nuclear Proteins; Parkinson Disease; Polymorphism, Single Nucleotide; Tumor Suppressor Proteins}},
language = {{eng}},
number = {{3}},
pages = {{294--303}},
publisher = {{Nature Publishing Group}},
series = {{Nature Genetics}},
title = {{Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture}},
url = {{http://dx.doi.org/10.1038/s41588-021-00785-3}},
doi = {{10.1038/s41588-021-00785-3}},
volume = {{53}},
year = {{2021}},
}