PROSPECT ConsortiumThe American Genome CenterInternational LBD Genomics ConsortiumInternational ALS/FTD ConsortiumKaivola, KarriChia, RuthDing, JinhuiJansson, LiljaLaaksovirta, HannuMyllykangas, Liisa2024-02-162024-02-162023-06-14PROSPECT Consortium, The American Genome Center, International LBD Genomics Consortium, International ALS/FTD Consortium, Kaivola, K, Chia, R, Ding, J, Jansson, L, Laaksovirta, H & Myllykangas, L 2023, 'Genome-wide structural variant analysis identifies risk loci for non-Alzheimer's dementias', Cell genomics, vol. 3, no. 6, 100316. https://doi.org/10.1016/j.xgen.2023.100316ORCID: /0000-0002-2237-5466/work/152345799ORCID: /0000-0003-1218-4014/work/152345875ORCID: /0000-0002-2380-8999/work/152350046http://hdl.handle.net/10138/571348We 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.21engcc_by_nc_ndinfo:eu-repo/semantics/openAccessamyotrophic lateral sclerosiscase-control studyfrontotemporal dementiagenome-wide association studyLewy body dementianon–Alzheimer's dementiaresourcestructural variantBiochemistry, cell and molecular biologyGenetics, developmental biology, physiologyArticleopenAccess70b3ea4d-61d1-4155-98fd-ba850217c08485161957826001101141900001