Whole-exome rare-variant analysis of Alzheimer's disease and related biomarker traits.
Details
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_763183AEC0D7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Whole-exome rare-variant analysis of Alzheimer's disease and related biomarker traits.
Journal
Alzheimer's & dementia
Working group(s)
Alzheimer's Disease Neuroimaging Initiative (ADNI), EMIF-AD Study Group
ISSN
1552-5279 (Electronic)
ISSN-L
1552-5260
Publication state
Published
Issued date
06/2023
Peer-reviewed
Oui
Volume
19
Number
6
Pages
2317-2331
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Despite increasing evidence of a role of rare genetic variation in the risk of Alzheimer's disease (AD), limited attention has been paid to its contribution to AD-related biomarker traits indicative of AD-relevant pathophysiological processes.
We performed whole-exome gene-based rare-variant association studies (RVASs) of 17 AD-related traits on whole-exome sequencing (WES) data generated in the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study (n = 450) and whole-genome sequencing (WGS) data from ADNI (n = 808).
Mutation screening revealed a novel probably pathogenic mutation (PSEN1 p.Leu232Phe). Gene-based RVAS revealed the exome-wide significant contribution of rare coding variation in RBKS and OR7A10 to cognitive performance and protection against left hippocampal atrophy, respectively.
The identification of these novel gene-trait associations offers new perspectives into the role of rare coding variation in the distinct pathophysiological processes culminating in AD, which may lead to identification of novel therapeutic and diagnostic targets.
We performed whole-exome gene-based rare-variant association studies (RVASs) of 17 AD-related traits on whole-exome sequencing (WES) data generated in the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery (EMIF-AD MBD) study (n = 450) and whole-genome sequencing (WGS) data from ADNI (n = 808).
Mutation screening revealed a novel probably pathogenic mutation (PSEN1 p.Leu232Phe). Gene-based RVAS revealed the exome-wide significant contribution of rare coding variation in RBKS and OR7A10 to cognitive performance and protection against left hippocampal atrophy, respectively.
The identification of these novel gene-trait associations offers new perspectives into the role of rare coding variation in the distinct pathophysiological processes culminating in AD, which may lead to identification of novel therapeutic and diagnostic targets.
Keywords
Humans, Alzheimer Disease/genetics, Alzheimer Disease/diagnosis, Exome/genetics, Genetic Association Studies, Phenotype, Biomarkers, Alzheimer's disease, biomarkers, endophenotypes, rare coding variants, whole-exome sequencing
Pubmed
Web of science
Open Access
Yes
Create date
12/12/2022 11:22
Last modification date
14/12/2023 7:19
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