Browsing by Author "Menon, Vilas"

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    Genome-wide structural variant analysis identifies risk loci for non-Alzheimer's dementias
    (Elsevier, 2023-05-04) Kaivola, Karri; 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; American Genome Center; International LBD Genomics Consortium; International ALS/FTD Consortium; PROSPECT Consortium; 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.; Medical and Molecular Genetics, School of Medicine
    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.
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    New directions for Alzheimer's disease research from the Jackson Laboratory Center for Alzheimer's and Dementia Research 2022 workshop
    (Wiley, 2024-03-10) Telpoukhovskaia, Maria A.; Murdy, Thomas J.; Marola, Olivia J.; Charland, Kevin; MacLean, Michael; Luquez, Tain; Lish, Alexandra M.; Neuner, Sarah; Dunn, Amy; Onos, Kristen D.; Wiley, Jesse; Archer, Derek; Huentelman, Matthew J.; Arnold, Matthias; Menon, Vilas; Goate, Alison; Van Eldik, Linda J.; Territo, Paul R.; Howell, Gareth R.; Carter, Gregory W.; O’Connell, Kristen M. S.; Kaczorowski, Catherine C.; 2022 JAX CADR Workshop; Medicine, School of Medicine
    Introduction: In September 2022, The Jackson Laboratory Center for Alzheimer's and Dementia Research (JAX CADR) hosted a workshop with leading researchers in the Alzheimer's disease and related dementias (ADRD) field. Methods: During the workshop, the participants brainstormed new directions to overcome current barriers to providing patients with effective ADRD therapeutics. The participants outlined specific areas of focus. Following the workshop, each group used standard literature search methods to provide background for each topic. Results: The team of invited experts identified four key areas that can be collectively addressed to make a significant impact in the field: (1) Prioritize the diversification of disease targets, (2) enhance factors promoting resilience, (3) de-risk clinical pipeline, and (4) centralize data management. Discussion: In this report, we review these four objectives and propose innovations to expedite ADRD therapeutic pipelines.