Amyotrophic lateral sclerosis and cerebellum.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
22 07 2022
Historique:
received: 12 04 2022
accepted: 15 07 2022
entrez: 22 7 2022
pubmed: 23 7 2022
medline: 27 7 2022
Statut: epublish

Résumé

Amyotrophic lateral sclerosis (ALS) is a devastating, heterogeneous neurodegenerative neuromuscular disease that leads to a fatal outcome within 2-5 years, and yet, a precise nature of the association between its major phenotypes and the cerebellar role in ALS pathology remains unknown. Recently, repeat expansions in several genes in which variants appreciably contribute to cerebellar pathology, including C9orf72, NIPA1, ATXN2 and ATXN1, have been found to confer a significant risk for ALS. To better define this relationship, we performed MAGMA gene-based analysis and tissue enrichment analysis using genome-wide association study summary statistics based on a study of 27,205 people with ALS and 110,881 controls. Our preliminary results imply a striking cerebellar tissue specificity and further support increasing calls for re-evaluation of the cerebellar role in the ALS pathology.

Identifiants

pubmed: 35869263
doi: 10.1038/s41598-022-16772-5
pii: 10.1038/s41598-022-16772-5
pmc: PMC9307771
doi:

Substances chimiques

C9orf72 Protein 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

12586

Subventions

Organisme : Medical Research Council
ID : MR/R024804/1
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : AL-CHALABI/APR15/844-791
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 103952/Z/14/Z
Pays : United Kingdom
Organisme : Department of Health
ID : NIHR202421
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : ALCHALABI-DOBSON/APR14/829-791
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L501529/1
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

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Auteurs

Renata Kabiljo (R)

Department of Biostatistics and Health Informatics, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. renata.kabiljo@kcl.ac.uk.

Alfredo Iacoangeli (A)

Department of Biostatistics and Health Informatics, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.

Ammar Al-Chalabi (A)

Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 9NU, UK.

Ivana Rosenzweig (I)

Department of Neuroimaging, Sleep and Brain Plasticity Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.

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Classifications MeSH