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

Cell genomics

Authors	Karri Kaivola Ruth Chia Jinhui Ding Memoona Rasheed Masashi Fujita Vilas Menon Ronald Walton Ryan Collins Kimberley Billingsley Harrison Brand Michael Talkowski Xuefang Zhao Ramita Dewan Ali Stark Anindita Ray Sultana Solaiman Pilar Jerez Laksh Malik Ted Dawson Liana Rosenthal Marilyn Albert Olga Pletnikova Juan Troncoso Mario Masellis Julia Keith Sandra Black Luigi Ferrucci Susan Resnick Toshiko Tanaka Eric Topol Ali Torkamani Pentti Tienari Tatiana Foroud Bernardino Ghetti John Landers Mina Ryten Huw Morris John Hardy Letizia Mazzini Sandra D'Alfonso Cristina Moglia Andrea Calvo Geidy Serrano Thomas Beach Tanis Ferman Neill Graff-Radford Bradley Boeve Zbigniew Wszolek Dennis Dickson Adriano Chio David Bennett Philip De Jager Owen Ross Clifton Dalgard Raphael Gibbs Bryan Traynor Sonja Scholz American Genome Center International LBD Genomics Consortium International ALS/FTD Consortium PROSPECT Consortium
Keywords	Lewy body dementia Amyotrophic Lateral Sclerosis case-control study Frontotemporal Dementia Genome-Wide Association Study non–Alzheimer's dementia resource structural variant
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 as a novel risk locus for LBD and detected the known structural variants at the and 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.
Year of Publication	2023
Journal	Cell genomics
Volume	3
Issue	6
Pages	100316
Date Published	06/2023
ISSN	2666-979X
DOI	10.1016/j.xgen.2023.100316
PubMed ID	37388914
Links	PubMed Google Scholar DOI

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