TY - JOUR
T1 - Genome-wide structural variant analysis identifies risk loci for non-Alzheimer's dementias
AU - PROSPECT Consortium
AU - The American Genome Center
AU - International LBD Genomics Consortium
AU - International ALS/FTD Consortium
AU - Kaivola, Karri
AU - Chia, Ruth
AU - Ding, Jinhui
AU - Rasheed, Memoona
AU - Fujita, Masashi
AU - Menon, Vilas
AU - Walton, Ronald L.
AU - Collins, Ryan L.
AU - Billingsley, Kimberley
AU - Brand, Harrison
AU - Talkowski, Michael
AU - Zhao, Xuefang
AU - Dewan, Ramita
AU - Stark, Ali
AU - Ray, Anindita
AU - Solaiman, Sultana
AU - Alvarez Jerez, Pilar
AU - Malik, Laksh
AU - Dawson, Ted M.
AU - Rosenthal, Liana S.
AU - Albert, Marilyn S.
AU - Pletnikova, Olga
AU - Troncoso, Juan C.
AU - Masellis, Mario
AU - Keith, Julia
AU - Black, Sandra E.
AU - Ferrucci, Luigi
AU - Resnick, Susan M.
AU - Tanaka, Toshiko
AU - Soltis, Anthony R.
AU - Viollet, Coralie
AU - Sukumar, Gauthaman
AU - Alba, Camille
AU - Lott, Nathaniel
AU - McGrath Martinez, Elisa
AU - Tuck, Meila
AU - Singh, Jatinder
AU - Bacikova, Dagmar
AU - Zhang, Xijun
AU - Hupalo, Daniel N.
AU - Adeleye, Adelani
AU - Wilkerson, Matthew D.
AU - Pollard, Harvey B.
AU - Dalgard, Clifton L.
AU - Gan-Or, Ziv
AU - Rogaeva, Ekaterina
AU - Brice, Alexis
AU - Lesage, Suzanne
AU - Xiromerisiou, Georgia
AU - D'Alfonso, Sandra
N1 - Publisher Copyright:
© 2023
PY - 2023/6/14
Y1 - 2023/6/14
N2 - 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.
AB - 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.
KW - Lewy body dementia
KW - amyotrophic lateral sclerosis
KW - case-control study
KW - frontotemporal dementia
KW - genome-wide association study
KW - non–Alzheimer's dementia
KW - resource
KW - structural variant
UR - https://www.scopus.com/pages/publications/85161957826
U2 - 10.1016/j.xgen.2023.100316
DO - 10.1016/j.xgen.2023.100316
M3 - Article
SN - 2666-979X
VL - 3
JO - Cell Genomics
JF - Cell Genomics
IS - 6
M1 - 100316
ER -