@article{10902/33363,
year = {2024},
url = {https://hdl.handle.net/10902/33363},
abstract = {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.},
publisher = {Elsevier (Cell Press)},
publisher = {Neuron, 2024, 112, 1-15},
title = {Genome sequence analyses identify novel risk loci for multiple system atrophy},
author = {Chia, Ruth and Ray, Anindita and Shah, Zalak and Ding, Jinhui and Ruffo, Paola and Fujita, Masashi and Menon, Vilas and Saez-Atienzar, Sara and Reho, Paolo and Kaivola, Karri and Walton, Ronald L. and Reynolds, Regina H. and Karra, Ramita and Sait, Shaimaa and Akcimen, Fulya and Diez-Fairen, Monica and Infante Ceberio, Jon and Lage Martínez, Carmen and Sánchez-Juan, Pascual},
}