Kaivola, K;
Chia, R;
Ding, J;
Rasheed, M;
Fujita, M;
Menon, V;
Walton, RL;
... Lopez, G; + view all
(2023)
Genome-wide structural variant analysis identifies risk loci for non-Alzheimer's dementias.
Cell Genomics
, 3
(6)
, Article 100316. 10.1016/j.xgen.2023.100316.
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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.
| Type: | Article |
|---|---|
| Title: | Genome-wide structural variant analysis identifies risk loci for non-Alzheimer's dementias |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.xgen.2023.100316 |
| Publisher version: | https://doi.org/10.1016/j.xgen.2023.100316 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Lewy body dementia, frontotemporal dementia, amyotrophic lateral sclerosis, structural variant, genome-wide association study, resource, case-control study, non–Alzheimer's dementia |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10172559 |
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