Evidence map›Paper›PMID 28586827›Full record

ArticleJAMA neurology2017

Genome-wide Pleiotropy Between Parkinson Disease and Autoimmune Diseases.

Aree Witoelar, Iris E Jansen, Yunpeng Wang, Rahul S Desikan, J Raphael Gibbs, Cornelis Blauwendraat, Wesley K Thompson, Dena G Hernandez, Srdjan Djurovic, Andrew J Schork and 18 more

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

Article in JAMA neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 205 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
205citing papers in PubMed, 11 pooled it
18.8field-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

205 citing papers in PubMed, 11 syntheses or guidelines pooled it, 374 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Pooled it
  11. Pooled it
  12. Article
  13. Article
  14. Is there a link between multiple sclerosis and Alzheimer disease? A critical note.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  15. Article
  16. Progress of Immunotherapies in Parkinson's Disease.CNS neuroscience & therapeutics · 2026
    Review
  17. Shared Epitope-PositiveNeurology(R) neuroimmunology & neuroinflammation · 2026
    Article
  18. Review
  19. Article
  20. Article

145 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors at 13 institutions in 6 countries.

Aree WitoelarNorwegian Centre for Mental Disorders Research (NORMENT), K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo2Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Iris E JansenDepartment of Clinical Genetics, Vrije Universiteit (VU) University Medical Center, Amsterdam, the Netherlands4German Center for Neurodegenerative Diseases (DZNE), Tübingen.
Yunpeng WangNorwegian Centre for Mental Disorders Research (NORMENT), K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo5Multimodal Imaging Laboratory, University of California at San Diego, La Jolla.
Rahul S DesikanMultimodal Imaging Laboratory, University of California at San Diego, La Jolla6Department of Radiology and Biomedical Imaging, University of California, San Francisco.
J Raphael GibbsLaboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland.
Cornelis BlauwendraatGerman Center for Neurodegenerative Diseases (DZNE), Tübingen.
Wesley K ThompsonDepartment of Psychiatry, University of California at San Diego, La Jolla9Department of Psychiatry, University of Copenhagen, Copenhagen, Denmark.
Dena G HernandezLaboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland.
Srdjan DjurovicNorwegian Centre for Mental Disorders Research (NORMENT), K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo10Department of Medical Genetics, University of Oslo, Oslo, Norway11Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Andrew J SchorkMultimodal Imaging Laboratory, University of California at San Diego, La Jolla12Sciences Graduate Program, University of California at San Diego, La Jolla13Department of Neurosciences, University of California at San Diego, La Jolla.
Francesco BettellaNorwegian Centre for Mental Disorders Research (NORMENT), K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo.
David EllinghausInstitute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
Andre FrankeInstitute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
Benedicte A LieDepartment of Medical Genetics, University of Oslo, Oslo, Norway11Department of Medical Genetics, Oslo University Hospital, Oslo, Norway15K. G. Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Oslo, Norway16Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway17Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Linda K McEvoyMultimodal Imaging Laboratory, University of California at San Diego, La Jolla15K. G. Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Oslo, Norway.
Tom H KarlsenK. G. Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Oslo, Norway16Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway18Division of Gastroenterology, Institute of Medicine, University of Bergen, Bergen, Norway19Norwegian Primary Sclerosing Cholangitis (PSC) Research Center, Department of Transplantation Medicine, Oslo.
Suzanne LesageSorbonne Universités, Université Pierre-et-Marie Curie (UPMC) Paris 06, UM 1127, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France21Institut National de la Santé et de la Récherche Médicale (INSERM), Unité 1127, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France22Centre National de la Recherche Scientifique (CNRS) UMR 7225, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France23Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France24Assistance Publique-Hôpitaux de Paris, Hôpital de la Salpêtrière, Département de Génétique et Cytogénétique, Paris, France.
Huw R MorrisDepartment of Clinical Neuroscience, National Hospital for Neurology and Neurosurgery (NHNN), University College London, London, England.
Alexis BriceSorbonne Universités, Université Pierre-et-Marie Curie (UPMC) Paris 06, UM 1127, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France21Institut National de la Santé et de la Récherche Médicale (INSERM), Unité 1127, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France22Centre National de la Recherche Scientifique (CNRS) UMR 7225, Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France23Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France24Assistance Publique-Hôpitaux de Paris, Hôpital de la Salpêtrière, Département de Génétique et Cytogénétique, Paris, France.
Nicholas W WoodDepartment of Molecular Neurosciences, Institute of Neurology, University College London, London, England.
Peter HeutinkDepartment of Clinical Genetics, Vrije Universiteit (VU) University Medical Center, Amsterdam, the Netherlands4German Center for Neurodegenerative Diseases (DZNE), Tübingen27Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
John HardyRita Lila Weston Institute, University College London, London, England.
Andrew B SingletonLaboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland.
Anders M DaleMultimodal Imaging Laboratory, University of California at San Diego, La Jolla8Department of Psychiatry, University of California at San Diego, La Jolla13Department of Neurosciences, University of California at San Diego, La Jolla29Department of Radiology, University of California at San Diego, La Jolla.
Thomas GasserGerman Center for Neurodegenerative Diseases (DZNE), Tübingen27Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Ole A AndreassenNorwegian Centre for Mental Disorders Research (NORMENT), K. G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo.
Manu SharmaDepartment of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany30Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
International Parkinson’s Disease Genomics Consortium (IPDGC), North American Brain Expression Consortium (NABEC), and United Kingdom Brain Expression Consortium (UKBEC) Investigators
German Center for Neurodegenerative Diseases · DEOslo University Hospital · NOUniversity of California San Diego · USNational Institute on Aging · USCentre National de la Recherche Scientifique · FRChristian-Albrechts-Universität zu Kiel · DEUniversity of Oslo · NOHertie Institute for Clinical Brain Research · DENational Hospital for Neurology and Neurosurgery · GBNeurosciences Institute · USUniversity College London · GBUniversity of California, San Francisco · USUniversity of Copenhagen · DK

Funding

Polygenicity, Pleiotrophy and Power: Novel Statistical Methods for Gene DiscoveryR01GM104400 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI THOMPSON, WESLEY KURT · 2014 to 2017
$1.6M
Medical Research Council G0700943Medical Research Council G0701075Medical Research Council G1100643NIGMS NIH HHS R01 GM104400Parkinson's UK G-0907Parkinson's UK J-0901Parkinson's UK K-1501
6 · The paper itself

Abstract

Importance: Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an association between immune-mediated diseases and Parkinson disease (PD). The post-GWAS era provides an opportunity for cross-phenotype analyses between different complex phenotypes. Objectives: To test the hypothesis that there are common genetic risk variants conveying risk of both PD and autoimmune diseases (ie, pleiotropy) and to identify new shared genetic variants and their pathways by applying a novel statistical framework in a genome-wide approach. Design, Setting, and Participants: Using the conjunction false discovery rate method, this study analyzed GWAS data from a selection of archetypal autoimmune diseases among 138 511 individuals of European ancestry and systemically investigated pleiotropy between PD and type 1 diabetes, Crohn disease, ulcerative colitis, rheumatoid arthritis, celiac disease, psoriasis, and multiple sclerosis. NeuroX data (6927 PD cases and 6108 controls) were used for replication. The study investigated the biological correlation between the top loci through protein-protein interaction and changes in the gene expression and methylation levels. The dates of the analysis were June 10, 2015, to March 4, 2017. Main Outcomes and Measures: The primary outcome was a list of novel loci and their pathways involved in PD and autoimmune diseases. Results: Genome-wide conjunctional analysis identified 17 novel loci at false discovery rate less than 0.05 with overlap between PD and autoimmune diseases, including known PD loci adjacent to GAK, HLA-DRB5, LRRK2, and MAPT for rheumatoid arthritis, ulcerative colitis and Crohn disease. Replication confirmed the involvement of HLA, LRRK2, MAPT, TRIM10, and SETD1A in PD. Among the novel genes discovered, WNT3, KANSL1, CRHR1, BOLA2, and GUCY1A3 are within a protein-protein interaction network with known PD genes. A subset of novel loci was significantly associated with changes in methylation or expression levels of adjacent genes. Conclusions and Relevance: The study findings provide novel mechanistic insights into PD and autoimmune diseases and identify a common genetic pathway between these phenotypes. The results may have implications for future therapeutic trials involving anti-inflammatory agents.

Indexed as

Genetic PleiotropyGenetic Predisposition to DiseaseGenome-Wide Association StudyArthritis, RheumatoidAutoimmune DiseasesCeliac DiseaseColitis, UlcerativeCrohn DiseaseDiabetes Mellitus, Type 1Genetic LociHumansMultiple SclerosisParkinson DiseasePsoriasisRisk Factors

Identifiers

PMID28586827
PMCPMC5710535
OpenAlexW2622719965

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.