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Neuron · 2024

Genome sequence analyses identify novel risk loci for multiple system atrophy.

СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Chia Ruth, Ray Anindita, Shah Zalak, Ding Jinhui, Ruffo Paola, Fujita Masashi, Menon Vilas, Saez-Atienzar Sara, Reho Paolo, Kaivola Karri, Walton Ronald L, Reynolds Regina H, Karra Ramita, Sait Shaimaa, Akcimen Fulya, Diez-Fairen Monica, Alvarez Ignacio, Fanciulli Alessandra, Stefanova Nadia, Seppi Klaus, Duerr Susanne, Leys Fabian, Krismer Florian, Sidoroff Victoria, Zimprich Alexander, Pirker Walter, Rascol Olivier, Foubert-Samier Alexandra, Meissner Wassilios G, Tison François, Pavy-Le Traon Anne, Pellecchia Maria Teresa, Barone Paolo, Russillo Maria Claudia, Marín-Lahoz Juan, Kulisevsky Jaime, Torres Soraya, Mir Pablo, Periñán Maria Teresa, Proukakis Christos, Chelban Viorica, Wu Lesley, Goh Yee Y, Parkkinen Laura, Hu Michele T, Kobylecki Christopher, Saxon Jennifer A, Rollinson Sara, Garland Emily, Biaggioni Italo, Litvan Irene, Rubio Ileana, Alcalay Roy N, Kwei Kimberly T, Lubbe Steven J, Mao Qinwen, Flanagan Margaret E, Castellani Rudolph J, Khurana Vikram, Ndayisaba Alain, Calvo Andrea, Mora Gabriele, Canosa Antonio, Floris Gianluca, Bohannan Ryan C, Moore Anni, Norcliffe-Kaufmann Lucy, Palma Jose-Alberto, Kaufmann Horacio, Kim Changyoun, Iba Michiyo, Masliah Eliezer, Dawson Ted M, Rosenthal Liana S, Pantelyat Alexander, Albert Marilyn S, Pletnikova Olga, Troncoso Juan C, Infante Jon, Lage Carmen, Sánchez-Juan Pascual, Serrano Geidy E, Beach Thomas G, Pastor Pau, Morris Huw R, Albani Diego, Clarimon Jordi, Wenning Gregor K, Hardy John A, Ryten Mina, Topol Eric, Torkamani Ali, Chiò Adriano, Bennett David A, De Jager Philip L, Low Philip A, Singer Wolfgang, Cheshire William P, Wszolek Zbigniew K, Dickson Dennis W, Traynor Bryan J, Gibbs J Raphael, Dalgard Clifton L, Ross Owen A, Houlden Henry, Scholz Sonja W

Аннотация

Multiple system atrophy (MSA) is an adult-onset, sporadic synucleinopathy characterized by parkinsonism, cerebellar ataxia, and dysautonomia. The genetic architecture of MSA is poorly understood, and treatments are limited to supportive measures. Here, we performed a comprehensive analysis of whole genome sequence data from 888 European-ancestry MSA cases and 7,128 controls to systematically investigate the genetic underpinnings of this understudied neurodegenerative disease. We identified four significantly associated risk loci using a genome-wide association study approach. Transcriptome-wide association analyses prioritized USP38-DT, KCTD7, and lnc-KCTD7-2 as novel susceptibility genes for MSA within these loci, and single-nucleus RNA sequence analysis found that the associated variants acted as cis-expression quantitative trait loci for multiple genes across neuronal and glial cell types. In conclusion, this study highlights the role of genetic determinants in the pathogenesis of MSA, and the publicly available data from this study represent a valuable resource for investigating synucleinopathies.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты