Evidence map›Paper›PMID 35521889›Full record

ArticleBrain : a journal of neurology2022

ATXN2 intermediate expansions in amyotrophic lateral sclerosis.

Jonathan D Glass, Ramita Dewan, Jinhui Ding, J Raphael Gibbs, Clifton Dalgard, Pamela J Keagle, Shankaracharya, Alberto García-Redondo, Bryan J Traynor, Ruth Chia and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.9field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. From incidental cerebellar atrophy to progressive motor syndrome: a case within the spectrum of ATXN2-associated neurodegeneration.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
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  17. Observational
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  19. Localization of Potential Energy in Hydrogen Bonds of theInternational journal of molecular sciences · 2025
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 3 countries.

Jonathan D GlassDepartment of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Ramita DewanNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
Jinhui DingNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
J Raphael GibbsComputational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA.ORCID 0000-0002-6985-0658
Clifton DalgardUniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Pamela J KeagleDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
ShankaracharyaDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Alberto García-RedondoInstituto de Investigaciaon Hospital 12 de Octubre, Madrid, Spain.
Bryan J TraynorNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
Ruth ChiaNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
John E LandersDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
National Institute on Aging · USUniversity of Massachusetts Chan Medical School · USEmory University · USJohns Hopkins University · USResearch Institute Hospital 12 de Octubre · ESUniformed Services University of the Health Sciences · US

Funding

EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI GONZALEZ HERNANDEZ, GRACIELA · 2001 to 2020
$32.5M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
SCRIPPS TRANSLATIONAL SCIENCE INSTITUTE (UL1)UL1RR025774 · NCRR · SCRIPPS RESEARCH INSTITUTE, THE · PI TOPOL, ERIC JEFFREY · 2008 to 2011
$16.3M
Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7M
Genome wide SNP analysis in Amyotrophic Lateral SclerosisZIAAG000933 · NIA · NATIONAL INSTITUTE ON AGING · PI TRAYNOR, BRYAN · 2009 to 2025
$9.8M
National Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8M
Risk Factors, Pathology, and Clinical Expressions of ADRF1AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2014 to 2014
$6.0M
Identification of genes causative for familial ALS gene using exome sequencingR01NS073873 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LANDERS, JOHN E · 2011 to 2019
$4.6M
Genome wide SNP analysis in Parkinson's diseaseZ01AG000949 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW B · 2006 to 2008
$2.6M
Identification and Characterization of ALS/FTD Associated Variants Using Whole Genome SequencingR56NS073873 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LANDERS, JOHN E · 2020 to 2020
$586k
Intramural NIH HHS Z01 AG000949NCRR NIH HHS UL1 RR025774NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG017917NIA NIH HHS RF1 AG015819NIA NIH HHS U01 AG061356NINDS NIH HHS R01 NS073873NINDS NIH HHS R56 NS073873NINDS NIH HHS U24 NS072026
6 · The paper itself

Abstract

Intermediate CAG (polyQ) expansions in the gene ataxin-2 (ATXN2) are now recognized as a risk factor for amyotrophic lateral sclerosis. The threshold for increased risk is not yet firmly established, with reports ranging from 27 to 31 repeats. We investigated the presence of ATXN2 polyQ expansions in 9268 DNA samples collected from people with amyotrophic lateral sclerosis, amyotrophic lateral sclerosis with frontotemporal dementia, frontotemporal dementia alone, Lewy body dementia and age matched controls. This analysis confirmed ATXN2 intermediate polyQ expansions of ≥31 as a risk factor for amyotrophic lateral sclerosis with an odds ratio of 6.31. Expansions were an even greater risk for amyotrophic lateral sclerosis with frontotemporal dementia (odds ratio 27.59) and a somewhat lesser risk for frontotemporal dementia alone (odds ratio 3.14). There was no increased risk for Lewy body dementia. In a subset of 1362 patients with amyotrophic lateral sclerosis with complete clinical data, we could not confirm previous reports of earlier onset of amyotrophic lateral sclerosis or shorter survival in 25 patients with expansions. These new data confirm ≥31 polyQ repeats in ATXN2 increase the risk for amyotrophic lateral sclerosis, and also for the first time show an even greater risk for amyotrophic lateral sclerosis with frontotemporal dementia. The lack of a more aggressive phenotype in amyotrophic lateral sclerosis patients with expansions has implications for ongoing gene-silencing trials for amyotrophic lateral sclerosis.

Indexed as

Amyotrophic Lateral SclerosisFrontotemporal DementiaLewy Body DiseaseAtaxin-2HumansPhenotypeAtaxin-2ATXN2 protein, humanamyotrophic lateral sclerosisataxin-2frontotemporal dementiapolyQ expansion

Identifiers

PMID35521889
PMCPMC9890463
OpenAlexW4228996594

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.