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

Research output: Contribution to journalArticleScientificpeer-review


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.

Original languageEnglish
Article number100316
JournalCell genomics
Issue number6
Number of pages21
Publication statusPublished - 14 Jun 2023
MoE publication typeA1 Journal article-refereed

Bibliographical note

Publisher Copyright:
© 2023

Fields of Science

  • amyotrophic lateral sclerosis
  • case-control study
  • frontotemporal dementia
  • genome-wide association study
  • Lewy body dementia
  • non–Alzheimer's dementia
  • resource
  • structural variant
  • 1182 Biochemistry, cell and molecular biology
  • 1184 Genetics, developmental biology, physiology

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