Genome-wide structural variant analysis identifies risk loci for non-Alzheimer's dementias

PROSPECT Consortium, The American Genome Center, International LBD Genomics Consortium, International ALS/FTD Consortium, Karri Kaivola, Ruth Chia, Jinhui Ding, Lilja Jansson, Hannu Laaksovirta, Liisa Myllykangas

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Sammanfattning

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.

Originalspråkengelska
Artikelnummer100316
TidskriftCell genomics
Volym3
Nummer6
Antal sidor21
ISSN2666-979X
DOI
StatusPublicerad - 14 juni 2023
MoE-publikationstypA1 Tidskriftsartikel-refererad

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Vetenskapsgrenar

  • 1182 Biokemi, cell- och molekylärbiologi
  • 1184 Genetik, utvecklingsbiologi, fysiologi

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