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; SAMIER FOUBERT, Alexandra; MEISSNER, Wassilios; TISON, Francois; PAVY-LE TRAON, Anne; PELLECCHIA, Maria Teresa; BARONE, Paolo; RUSSILLO, Maria Claudia; MARIN-LAHOZ, Juan; KULISEVSKY, Jaime; TORRES, Soraya; MIR, Pablo; PERINAN, 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; SANCHEZ-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; CHIO, 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

doi:10.1016/j.neuron.2024.04.002

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Neuron. 2024-05-02

Resumen en inglés

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.< Leer menos

Palabras clave en inglés

GWAS

MSA

TWAS

Colocalization

Gene-Burden Analysis

Genome-Wide Association Study

Multiple System Atrophy

Pathway Analysis

Repeat Expansion Mapping

Transcriptome-Wide Association Study

Whole Genome Sequencing

URI

https://oskar-bordeaux.fr/handle/20.500.12278/200576

DOI

http://dx.doi.org/10.1016/j.neuron.2024.04.002

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Genome sequence analyses identify novel risk loci for multiple system atrophy

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Licencia de uso del documento

Genome sequence analyses identify novel risk loci for multiple system atrophy

Idioma

Este ítem está publicado en

Resumen en inglés

Palabras clave en inglés

URI

DOI

Centros de investigación