Genome-wide structural variant analysis identifies risk loci for non-Alzheimer's dementias
Kaivola, Karri Chia, Ruth Ding, Jinhui Rasheed, Memoona Fujita, Masashi Menon, Vilas Walton, Ronald L Collins, Ryan L Billingsley, Kimberley Brand, Harrison
Authors
Chia, Ruth
Ding, Jinhui
Rasheed, Memoona
Fujita, Masashi
Menon, Vilas
Walton, Ronald L
Collins, Ryan L
Billingsley, Kimberley
Brand, Harrison
Talkowski, Michael
Zhao, Xuefang
Dewan, Ramita
Stark, Ali
Ray, Anindita
Solaiman, Sultana
Alvarez Jerez, Pilar
Malik, Laksh
Dawson, Ted M
Rosenthal, Liana S
Albert, Marilyn S
Pletnikova, Olga
Troncoso, Juan C
Masellis, Mario
Keith, Julia
Black, Sandra E
Ferrucci, Luigi
Resnick, Susan M
Tanaka, Toshiko
Topol, Eric
Torkamani, Ali
Tienari, Pentti
Foroud, Tatiana M
Ghetti, Bernardino
Landers, John E
Ryten, Mina
Morris, Huw R
Hardy, John A
Mazzini, Letizia
D'Alfonso, Sandra
Moglia, Cristina
Calvo, Andrea
Serrano, Geidy E
Beach, Thomas G
Ferman, Tanis
Graff-Radford, Neill R
Boeve, Bradley F
Wszolek, Zbigniew K
Dickson, Dennis W
Chiò, Adriano
Bennett, David A
De Jager, Philip L
Ross, Owen A
Dalgard, Clifton L
Gibbs, J Raphael
Traynor, Bryan J
Scholz, Sonja W
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UMass Chan Affiliations
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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.
Source
Kaivola K, Chia R, Ding J, Rasheed M, Fujita M, Menon V, Walton RL, Collins RL, Billingsley K, Brand H, Talkowski M, Zhao X, Dewan R, Stark A, Ray A, Solaiman S, Alvarez Jerez P, Malik L, Dawson TM, Rosenthal LS, Albert MS, Pletnikova O, Troncoso JC, Masellis M, Keith J, Black SE, Ferrucci L, Resnick SM, Tanaka T; American Genome Center; International LBD Genomics Consortium; International ALS/FTD Consortium; PROSPECT Consortium; Topol E, Torkamani A, Tienari P, Foroud TM, Ghetti B, Landers JE, Ryten M, Morris HR, Hardy JA, Mazzini L, D'Alfonso S, Moglia C, Calvo A, Serrano GE, Beach TG, Ferman T, Graff-Radford NR, Boeve BF, Wszolek ZK, Dickson DW, Chiò A, Bennett DA, De Jager PL, Ross OA, Dalgard CL, Gibbs JR, Traynor BJ, Scholz SW. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer's dementias. Cell Genom. 2023 May 4;3(6):100316. doi: 10.1016/j.xgen.2023.100316. PMID: 37388914; PMCID: PMC10300553.