Evidence map›Paper›PMID 33107653›Full record

ArticleMovement disorders : official journal of the Movement Disorder Society2021

Shared Genetics of Multiple System Atrophy and Inflammatory Bowel Disease.

Alexey A Shadrin, Sören Mucha, David Ellinghaus, Mary B Makarious, Cornelis Blauwendraat, Ashwin A K Sreelatha, Antonio Heras-Garvin, Jinhui Ding, Monia Hammer, Alexandra Foubert-Samier and 27 more

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In one paragraph

Article in Movement disorders : official journal of the Movement Disorder Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.4field-weighted citation impact, top 14% 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

11 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. The genetic basis of multiple system atrophy.Journal of translational medicine · 2023
    Review
  7. Article
  8. Article
  9. A Mouse Model of Multiple System Atrophy: Bench to Bedside.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Review
  10. Article
  11. 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

37 authors at 10 institutions in 6 countries.

Alexey A ShadrinNORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.ORCID 0000-0002-7467-250X
Sören Mucha *Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
David Ellinghaus *Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Mary B MakariousNeurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and, Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Cornelis BlauwendraatLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Ashwin A K SreelathaCentre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
Antonio Heras-GarvinDepartment of Neurology, Medical University of Innsbruck, Innsbruck, Austria.ORCID 0000-0003-2231-2681
Jinhui DingLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Monia HammerLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0001-9693-2459
Alexandra Foubert-SamierService de Neurologie, CRMR Atrophie Multisystématisée, CHU Bordeaux, Bordeaux, France.
Wassilios G MeissnerService de Neurologie, CRMR Atrophie Multisystématisée, CHU Bordeaux, Bordeaux, France.ORCID 0000-0003-2172-7527
Olivier RascolCentre de Reference Maladie Rare Atrophie MultiSystématisée, Centre d'Investigation, Clinique CIC 1436, Services de Pharmacologie Clinique et Neurosciences, NeuroToul COEN Center, Toulouse, France.
Anne Pavy-Le TraonNeurology Department, French Reference Centre for MSA, University Hospital of Toulouse and INSERM U 1048, Institute of Cardiovascular and Metabolic Diseases, Toulouse, France.
Oleksandr FreiNORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Kevin S O'ConnellNORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Shahram BahramiNORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Stefan SchreiberInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Wolfgang LiebInstitute of Epidemiology and Biobank PopGen, Christian-Albrechts-University of Kiel, Kiel, Germany.
Martina Müller-NurasyidInstitute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
Ulf SchminkeDepartment of Neurology, University Medicine Greifswald, Greifswald, Germany.
Georg HomuthDepartment of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany.
Carsten O SchmidtInstitute for Community Medicine, Study of Health in Pomerania/KEF, University Medicine Greifswald, Greifswald, Germany.
Markus M NöthenInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Per HoffmannInstitute of Human Genetics, University of Bonn, Bonn, Germany.
Christian GiegerResearch Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Gregor WenningDepartment of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
European Multiple System Atrophy Study Group
J Raphael GibbsLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Andre FrankeInstitute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
John HardyRita Lila Weston Institute, University College London, London, UK.
Nadia StefanovaDepartment of Neurology, Medical University of Innsbruck, Innsbruck, Austria.ORCID 0000-0001-8188-639X
Thomas GasserGerman Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Andrew SingletonLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Henry HouldenRita Lila Weston Institute, University College London, London, UK.
Sonja W ScholzNeurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and, Stroke, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0002-6623-0429
Ole A AndreassenNORMENT, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Manu SharmaCentre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
National Institutes of Health · USOslo University Hospital · NOChristian-Albrechts-Universität zu Kiel · DEInnsbruck Medical University · ATInserm · FRUniversitätsmedizin Greifswald · DEHelmholtz Zentrum München · DEUniversity of Bonn · DEUniversity of Tübingen · DECentre National de la Recherche Scientifique · FR

Funding

Genetic characterization of atypical parkinsonismZIANS003154 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI SCHOLZ, SONJA · 2016 to 2025
$15.4M
Genome wide SNP analysis in Parkinson's diseaseZ01AG000949 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW B · 2006 to 2008
$2.6M
Intramural NIH HHS Z01 AG000949Intramural NIH HHS Z99 AG999999Intramural NIH HHS ZIA NS003154Medical Research Council MR/N026004/1Wellcome TrustWellcome Trust 202903/Z/16/Z
6 · The paper itself

Abstract

backgroundMultiple system atrophy (MSA) is a rare neurodegenerative disease characterized by intracellular accumulations of α-synuclein and nerve cell loss in striatonigral and olivopontocerebellar structures. Epidemiological and clinical studies have reported potential involvement of autoimmune mechanisms in MSA pathogenesis. However, genetic etiology of this interaction remains unknown. We aimed to investigate genetic overlap between MSA and 7 autoimmune diseases and to identify shared genetic loci.

methodsGenome-wide association study summary statistics of MSA and 7 autoimmune diseases were combined in cross-trait conjunctional false discovery rate analysis to explore overlapping genetic background. Expression of selected candidate genes was compared in transgenic MSA mice and wild-type mice. Genetic variability of candidate genes was further investigated using independent whole-exome genotyping data from large cohorts of MSA and autoimmune disease patients and healthy controls.

resultsWe observed substantial polygenic overlap between MSA and inflammatory bowel disease and identified 3 shared genetic loci with leading variants upstream of the DENND1B and RSP04 genes, and in intron of the C7 gene. Further, the C7 gene showed significantly dysregulated expression in the degenerating midbrain of transgenic MSA mice compared with wild-type mice and had elevated burden of protein-coding variants in independent MSA and inflammatory bowel disease cohorts.

conclusionOur study provides evidence of shared genetic etiology between MSA and inflammatory bowel disease with an important role of the C7 gene in both phenotypes, with the implication of immune and gut dysfunction in MSA pathophysiology. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Indexed as

Inflammatory Bowel DiseasesMultiple System Atrophyalpha-SynucleinAnimalsGenome-Wide Association StudyHumansMiceMice, Transgenicalpha-Synucleinconjunctional false discovery rategenetic overlapinflammatory bowel diseasemultiple system atrophy

Identifiers

PMID33107653
PMCPMC8985479
OpenAlexW3094630161

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Registered trials

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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.