Evidence map›Paper›PMID 35334234›Full record

ReviewThe Lancet. Neurology2022

Emerging insights into the complex genetics and pathophysiology of amyotrophic lateral sclerosis.

Stephen A Goutman, Orla Hardiman, Ammar Al-Chalabi, Adriano Chió, Masha G Savelieff, Matthew C Kiernan, Eva L Feldman

Open access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in The Lancet. Neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 241 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
241citing papers in PubMed, 3 pooled it
43.1field-weighted citation impact, top 1% 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

241 citing papers in PubMed, 3 syntheses or guidelines pooled it, 365 citations in OpenAlex.

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  5. Tofersen Treatment inMayo Clinic proceedings. Innovations, quality & outcomes · 2026
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181 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 5 countries.

Stephen A GoutmanDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.
Orla HardimanAcademic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Ammar Al-ChalabiDepartment of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, and Department of Neurology, King's College London, London, UK.
Adriano ChióRita Levi Montalcini Department of Neurosciences, University of Turin, Turin, Italy.
Masha G SavelieffDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.
Matthew C KiernanBrain and Mind Centre, University of Sydney, Sydney, NSW, Australia; Department of Neurology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Eva L FeldmanDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA. Electronic address: efeldman@umich.edu.
University of Michigan–Ann Arbor · USKing's College London · GBRoyal Prince Alfred Hospital · AUTrinity College Dublin · IEUniversity of Turin · IT

Funding

Mapping the ALS Exposome to Gain New Insights into Disease Risk and PathogenesisR01ES030049 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BATTERMAN, STUART A, FELDMAN, EVA LUCILLE · 2020 to 2024
$3.5M
Developing novel strategies for personalized treatment and prevention of ALS: Leveraging the global exposome, genome, epigenome, metabolome, and inflammasome with data science in a case/control cohortR01NS127188 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BATTERMAN, STUART A, FELDMAN, EVA LUCILLE · 2021 to 2024
$3.4M
Creating a foundation for personalized age- and sex-based immune-targeted therapies from an ALS longitudinal cohort by identifying peripheral and central immune signaturesR01NS120926 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GOUTMAN, STEPHEN, MURDOCK, BENJAMIN JOSEPH · 2021 to 2025
$3.0M
Metabolomic Signatures Linking ALS to Persistent Organic Pollutant ExposuresR01TS000289 · TS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FELDMAN, EVA LUCILLE · 2018 to 2020
$1.5M
Linking long-term air pollution exposure with inflammation, ALS risk, and disease progressionR01TS000327 · TS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FELDMAN, EVA LUCILLE, GOUTMAN, STEPHEN · 2021 to 2023
$1.4M
Impact of Geospatial Factors and Environmental Pollutants on Amyotrophic Lateral Sclerosis in the State of MichiganK23ES027221 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GOUTMAN, STEPHEN · 2017 to 2021
$1.0M
ATSDR CDC HHS R01 TS000289ATSDR CDC HHS R01 TS000327Medical Research Council MR/L501529/1Medical Research Council MR/R024804/1Motor Neurone Disease Association AL-CHALABI/APR15/844-791Motor Neurone Disease Association ALCHALABI-DOBSON/APR14/829-791NIEHS NIH HHS K23 ES027221NIEHS NIH HHS R01 ES030049NINDS NIH HHS R01 NS120926NINDS NIH HHS R01 NS127188
6 · The paper itself

Abstract

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease. The discovery of genes associated with amyotrophic lateral sclerosis, commencing with SOD1 in 1993, started fairly gradually. Recent advances in genetic technology have led to the rapid identification of multiple new genes associated with the disease, and to a new understanding of oligogenic and polygenic disease risk. The overlap of genes associated with amyotrophic lateral sclerosis with those of other neurodegenerative diseases is shedding light on the phenotypic spectrum of neurodegeneration, leading to a better understanding of genotype-phenotype correlations. A deepening knowledge of the genetic architecture is allowing the characterisation of the molecular steps caused by various mutations that converge on recurrent dysregulated pathways. Of crucial relevance, mutations associated with amyotrophic lateral sclerosis are amenable to novel gene-based therapeutic options, an approach in use for other neurological illnesses. Lastly, the exposome-the summation of lifetime environmental exposures-has emerged as an influential component for amyotrophic lateral sclerosis through the gene-time-environment hypothesis. Our improved understanding of all these aspects will lead to long-awaited therapies and the identification of modifiable risks factors.

Indexed as

Amyotrophic Lateral SclerosisNeurodegenerative DiseasesGenetic Association StudiesHumansMutation

Identifiers

PMID35334234
PMCPMC9513754
OpenAlexW4220726928

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.