Evidence map›Paper›PMID 35042540›Full record

ArticleGenome medicine2022

Functional characterisation of the amyotrophic lateral sclerosis risk locus GPX3/TNIP1.

Restuadi Restuadi, Frederik J Steyn, Edor Kabashi, Shyuan T Ngo, Fei-Fei Cheng, Marta F Nabais, Mike J Thompson, Ting Qi, Yang Wu, Anjali K Henders and 20 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.6field-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

24 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review of the Pathology of Muscle in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2026
    Review
  7. Article
  8. Article
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  12. Article
  13. Article
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  15. Review
  16. METTL3-dependent mCell death & disease · 2024
    Article
  17. Article
  18. Review
  19. Article
  20. Review
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

30 authors at 11 institutions in 7 countries.

Restuadi RestuadiInstitute for Molecular Bioscience, The University of Queensland, QLD, Brisbane, 4072, Australia.
Frederik J SteynSchool of Biomedical Sciences, The University of Queensland, QLD, Brisbane, 4072, Australia.
Edor KabashiImagine Institute, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 1163, Paris Descartes Université, 75015, Paris, France.
Shyuan T NgoCentre for Clinical Research, The University of Queensland, QLD, Brisbane, 4019, Australia.
Fei-Fei ChengInstitute for Molecular Bioscience, The University of Queensland, QLD, Brisbane, 4072, Australia.
Marta F NabaisInstitute for Molecular Bioscience, The University of Queensland, QLD, Brisbane, 4072, Australia.
Mike J ThompsonDepartment of Computer Science, University of California Los Angeles, Los Angeles, CA, USA.
Ting QiInstitute for Molecular Bioscience, The University of Queensland, QLD, Brisbane, 4072, Australia.
Yang WuInstitute for Molecular Bioscience, The University of Queensland, QLD, Brisbane, 4072, Australia.
Anjali K HendersInstitute for Molecular Bioscience, The University of Queensland, QLD, Brisbane, 4072, Australia.
Leanne WallaceInstitute for Molecular Bioscience, The University of Queensland, QLD, Brisbane, 4072, Australia.
Chris R ByeFlorey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, 3052, Australia.
Bradley J TurnerFlorey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, 3052, Australia.
Laura ZiserInstitute for Molecular Bioscience, The University of Queensland, QLD, Brisbane, 4072, Australia.
Susan MathersCalvary Health Care Bethlehem, Parkdale, VIC, 3195, Australia.
Pamela A McCombeDepartment of Neurology, Royal Brisbane and Women's Hospital, QLD, Brisbane, 4029, Australia.
Merrilee NeedhamFiona Stanley Hospital, Perth, WA, 6150, Australia.
David SchultzDepartment of Neurology, Flinders Medical Centre, Bedford Park, SA, 5042, Australia.
Matthew C KiernanBrain & Mind Centre, University of Sydney, Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, Sydney, NSW, 2006, Australia.
Wouter van RheenenDepartment of Neurology, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.
Leonard H van den BergDepartment of Neurology, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.
Jan H VeldinkDepartment of Neurology, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.
Roel OphoffDepartment of Computer Science, University of California Los Angeles, Los Angeles, CA, USA.
Alexander GusevDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Noah ZaitlenDepartment of Computer Science, University of California Los Angeles, Los Angeles, CA, USA.
Allan F McRaeInstitute for Molecular Bioscience, The University of Queensland, QLD, Brisbane, 4072, Australia.
Robert D HendersonDepartment of Neurology, Royal Brisbane and Women's Hospital, QLD, Brisbane, 4029, Australia.
Naomi R WrayInstitute for Molecular Bioscience, The University of Queensland, QLD, Brisbane, 4072, Australia.
Jean GiacomottoQueensland Brain Institute, The University of Queensland, QLD, Brisbane, 4072, Australia.
Fleur C GartonInstitute for Molecular Bioscience, The University of Queensland, QLD, Brisbane, 4072, Australia. f.garton@uq.edu.au.ORCID 0000-0002-1490-5930
The University of Queensland · AUAllen Institute for Brain Science · USUniversity of California, Los Angeles · USUtrecht University · NLThe University of Melbourne · AUBrigham and Women's Hospital · USCalvary Health Care Bethlehem · AUCentre National de la Recherche Scientifique · FRFlinders University · AUThe University of Sydney · AUUniversity of Notre Dame · US

Funding

Training Grant in Genomic Analysis and InterpretationT32HG002536 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Valerie A Arboleda, Harold Pimentel · 2002 to 2026
$8.6M
Joint genomic and statistical analyses of schizophrenia and bipolar to decipher genetic susceptibilityR01MH115676 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Roel A Ophoff, Bogdan Pasaniuc · 2018 to 2026
$5.9M
NHGRI NIH HHS T32 HG002536NIMH NIH HHS R01 MH115676
6 · The paper itself

Abstract

backgroundAmyotrophic lateral sclerosis (ALS) is a complex, late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies (GWAS) have identified ten risk loci to date, including the TNIP1/GPX3 locus on chromosome five. Given association analysis data alone cannot determine the most plausible risk gene for this locus, we undertook a comprehensive suite of in silico, in vivo and in vitro studies to address this.

methodsThe Functional Mapping and Annotation (FUMA) pipeline and five tools (conditional and joint analysis (GCTA-COJO), Stratified Linkage Disequilibrium Score Regression (S-LDSC), Polygenic Priority Scoring (PoPS), Summary-based Mendelian Randomisation (SMR-HEIDI) and transcriptome-wide association study (TWAS) analyses) were used to perform bioinformatic integration of GWAS data (N

resultsSMR analyses implicated both TNIP1 and GPX3 (p < 1.15 × 10

conclusionsThese results support GPX3 as a lead ALS risk gene in this locus, with more data needed to confirm/reject a role for TNIP1. This has implications for understanding disease mechanisms (GPX3 acts in the same pathway as SOD1, a well-established ALS-associated gene) and identifying new therapeutic approaches. Few previous examples of in-depth investigations of risk loci in ALS exist and a similar approach could be applied to investigate future expected GWAS findings.

Indexed as

Amyotrophic Lateral SclerosisNeurodegenerative DiseasesAnimalsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideZebrafishComputational biologyDisease progressionGenesGenome-wide association studyMNDMotor neurone diseaseNeurodegenerative diseasesQuantitative trait lociRegulatorZebrafish

Identifiers

PMID35042540
PMCPMC8767698
OpenAlexW4205449517

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.