作者
Wouter van Rheenen, Rick AA van der Spek, Mark K Bakker, Joke JFA van Vugt, Paul J Hop, Ramona AJ Zwamborn, Niek de Klein, Harm-Jan Westra, Olivier B Bakker, Patrick Deelen, Gemma Shireby, Eilis Hannon, Matthieu Moisse, Denis Baird, Restuadi Restuadi, Egor Dolzhenko, Annelot M Dekker, Klara Gawor, Henk-Jan Westeneng, Gijs HP Tazelaar, Kristel R van Eijk, Maarten Kooyman, Ross P Byrne, Mark Doherty, Mark Heverin, Ahmad Al Khleifat, Alfredo Iacoangeli, Aleksey Shatunov, Nicola Ticozzi, Johnathan Cooper-Knock, Bradley N Smith, Marta Gromicho, Siddharthan Chandran, Suvankar Pal, Karen E Morrison, Pamela J Shaw, John Hardy, Richard W Orrell, Michael Sendtner, Thomas Meyer, Nazli Basak, Anneke J van der Kooi, Antonia Ratti, Isabella Fogh, Cinzia Gellera, Giuseppe Lauria, Stefania Corti, Cristina Cereda, Daisy Sproviero, Sandra D'Alfonso, Gianni Soraru, Gabriele Siciliano, Massimiliano Filosto, Alessandro Padovani, Adriano Chio, Calvo
发表日期
2021
期刊
Nature Genetics
出版商
Nature Research
简介
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature …
学术搜索中的文章
W Van Rheenen, RAA Van Der Spek, MK Bakker… - Nature genetics, 2021