Genome-wide structural variant analysis identifies risk loci for non-Alzheimer's dementias
Author(s)
Type
Journal Article
Abstract
We characterized the role of structural variants, a largely unexplored type of genetic variation, in two non-Alzheimer's dementias, namely Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced structural variant calling pipeline (GATK-SV) to short-read whole-genome sequence data from 5,213 European-ancestry cases and 4,132 controls. We discovered, replicated, and validated a deletion in TPCN1 as a novel risk locus for LBD and detected the known structural variants at the C9orf72 and MAPT loci as associated with FTD/ALS. We also identified rare pathogenic structural variants in both LBD and FTD/ALS. Finally, we assembled a catalog of structural variants that can be mined for new insights into the pathogenesis of these understudied forms of dementia.
Date Issued
2023-06-14
Date Acceptance
2023-04-06
Citation
Cell Genomics, 2023, 3 (6)
ISSN
2666-979X
Publisher
Elsevier
Journal / Book Title
Cell Genomics
Volume
3
Issue
6
Copyright Statement
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/37388914
Subjects
amyotrophic lateral sclerosis
case-control study
frontotemporal dementia
genome-wide association study
Lewy body dementia
non–Alzheimer's dementia
resource
structural variant
Publication Status
Published
Coverage Spatial
United States
Article Number
100316
Date Publish Online
2023-05-04