Evidence map›Paper›PMID 31701892›Full record

SynthesisThe Lancet. Neurology2019

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies.

Mike A Nalls, Cornelis Blauwendraat, Costanza L Vallerga, Karl Heilbron, Sara Bandres-Ciga, Diana Chang, Manuela Tan, Demis A Kia, Alastair J Noyce, Angli Xue and 44 more

Open access · greenAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The Lancet. Neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,472 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,472citing papers in PubMed, 7 pooled it
154.2field-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

1,472 citing papers in PubMed, 7 syntheses or guidelines pooled it, 2,465 citations in OpenAlex.

  1. Genetic Landscape of Monogenic Parkinson's Disease in the African Population-A Systematic Review.Movement disorders : official journal of the Movement Disorder Society · 2026
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  11. Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026
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  19. Eating Disorders and Parkinson's Disease-2: Genetic Epidemiology and Shared Genomics.European eating disorders review : the journal of the Eating Disorders Association · 2026
    Article
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1,412 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

54 authors at 20 institutions in 9 countries.

Mike A NallsLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Data Tecnica International, Glen Echo, MD, USA. Electronic address: mike@datatecnica.com.
Cornelis BlauwendraatLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Costanza L VallergaInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Karl Heilbron23andMe, Sunnyvale, CA, USA.
Sara Bandres-CigaLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Diana ChangDepartment of Human Genetics, Genentech, South San Francisco, CA, USA.
Manuela TanDepartment of Molecular Neuroscience, UCL Queen Square Institute of Neurology, London, UK; Department of Clinical and Movement Neuroscience and UCL Movement Disorders Centre, UCL Queen Square Institute of Neurology, London, UK.
Demis A KiaDepartment of Molecular Neuroscience, UCL Queen Square Institute of Neurology, London, UK; Department of Clinical and Movement Neuroscience and UCL Movement Disorders Centre, UCL Queen Square Institute of Neurology, London, UK.
Alastair J NoyceDepartment of Molecular Neuroscience, UCL Queen Square Institute of Neurology, London, UK; Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
Angli XueQueensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Jose BrasDepartment of Neurodegenerative Diseases, UCL Queen Square Institute of Neurology, London, UK; Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA.
Emily YoungDepartment of Neurology, Baylor College of Medicine, Houston, TX, USA.
Rainer von CoellnDepartment of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA.
Javier Simón-SánchezDepartment for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases, Tübingen, Germany.
Claudia SchulteDepartment for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases, Tübingen, Germany.
Manu SharmaCentre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
Lynne KrohnDepartment of Human Genetics, McGill University, Montreal, QC, Canada; Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Lasse PihlstrømDepartment of Neurology, Oslo University Hospital, Oslo, Norway.
Ari SiitonenInstitute of Clinical Medicine, Department of Neurology, University of Oulu, Oulu, Finland; Department of Neurology and Medical Research Center, Oulu University Hospital, Oulu, Finland.
Hirotaka IwakiLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Data Tecnica International, Glen Echo, MD, USA; The Michael J Fox Foundation, New York, NY, USA.
Hampton LeonardLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Data Tecnica International, Glen Echo, MD, USA.
Faraz FaghriLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Department of Computer Science, University of Illinois Urbana-Champaign, Champaign, IL, USA.
J Raphael GibbsLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Dena G HernandezLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Sonja W ScholzNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA.
Juan A BotiaDepartment of Molecular Neuroscience, UCL Queen Square Institute of Neurology, London, UK; Departamento de Ingeniería de la Información y las Comunicaciones, Universidad de Murcia, Spain.
Maria MartinezInstitut national de la santé et de la recherche médicale Unité mixte de recherche 1220, Toulouse, France; Paul Sabatier University, Toulouse, France.
Jean-Christophe CorvolInstitut national de la santé et de la recherche médicale U1127, CNRS UMR 7225, Paris, France; Sorbonne Université centre national de la recherche médicale, unité mixte de recherche 1127, Paris, France; Assistance Publique Hôpitaux de Paris, Paris, France; Institut du Cerveau et de la Moelle épinière, Paris, France.
Suzanne LesageInstitut national de la santé et de la recherche médicale U1127, CNRS UMR 7225, Paris, France; Sorbonne Université centre national de la recherche médicale, unité mixte de recherche 1127, Paris, France; Assistance Publique Hôpitaux de Paris, Paris, France; Institut du Cerveau et de la Moelle épinière, Paris, France.
Joseph JankovicDepartment of Neurology, Baylor College of Medicine, Houston, TX, USA.
Lisa M ShulmanDepartment of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA.
Margaret SutherlandNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Pentti TienariClinical Neurosciences, Neurology, University of Helsinki, Helsinki, Finland; Helsinki University Hospital, Helsinki, Finland.
Kari MajamaaInstitute of Clinical Medicine, Department of Neurology, University of Oulu, Oulu, Finland; Department of Neurology and Medical Research Center, Oulu University Hospital, Oulu, Finland.
Mathias ToftDepartment of Neurology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Ole A AndreassenDivision of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Jebsen Centre for Psychosis Research, University of Oslo, Oslo, Norway.
Tushar BangaleDepartment of Human Genetics, Genentech, South San Francisco, CA, USA.
Alexis BriceInstitut national de la santé et de la recherche médicale U1127, CNRS UMR 7225, Paris, France; Sorbonne Université centre national de la recherche médicale, unité mixte de recherche 1127, Paris, France; Assistance Publique Hôpitaux de Paris, Paris, France; Institut du Cerveau et de la Moelle épinière, Paris, France.
Jian YangQueensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Ziv Gan-OrDepartment of Human Genetics, McGill University, Montreal, QC, Canada; Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
Thomas GasserDepartment for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases, Tübingen, Germany.
Peter HeutinkDepartment for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases, Tübingen, Germany.
Joshua M ShulmanDepartment of Neurology, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA.
Nicholas W WoodDepartment of Molecular Neuroscience, UCL Queen Square Institute of Neurology, London, UK; Department of Clinical and Movement Neuroscience and UCL Movement Disorders Centre, UCL Queen Square Institute of Neurology, London, UK.
David A Hinds23andMe, Sunnyvale, CA, USA.
John A HardyDepartment of Molecular Neuroscience, UCL Queen Square Institute of Neurology, London, UK.
Huw R MorrisDepartment of Clinical and Movement Neuroscience and UCL Movement Disorders Centre, UCL Queen Square Institute of Neurology, London, UK.
Jacob GrattenInstitute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia; Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia.
Peter M VisscherQueensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia; Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia.
Robert R GrahamDepartment of Human Genetics, Genentech, South San Francisco, CA, USA.
Andrew B SingletonLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
23andMe Research Team
System Genomics of Parkinson's Disease Consortium
International Parkinson's Disease Genomics Consortium
National Institutes of Health · USThe University of Queensland · AUNational Hospital for Neurology and Neurosurgery · GBCentre National de la Recherche Scientifique · FROslo University Hospital · NOQueen Mary University of London · GBGerman Center for Neurodegenerative Diseases · DEMontreal Neurological Institute and Hospital · CAUniversity of Maryland, Baltimore · USUniversité Toulouse III - Paul Sabatier · FRBaylor College of Medicine · USOulu University Hospital · FIHertie Institute for Clinical Brain Research · DEVan Andel Institute · US23andMe (United States) · USNational Institute of Neurological Disorders and Stroke · USData Tecnica International (United States) · USNational Institute on Aging · USUniversity College London · GBUniversity of Helsinki · FI

Funding

Dysfunction of the Autophagy-Lysosomal Pathway as a Common Mechanism of NeurodegenerationRF1AG058476 · NIA · J. DAVID GLADSTONE INSTITUTES · PI FINKBEINER, STEVEN M · 2017 to 2018
$4.1M
Intramural NIH HHS Z99 AG999999Medical Research Council G0700943Medical Research Council G0701075Medical Research Council G0901254Medical Research Council G1100643Medical Research Council MR/K01417X/1Medical Research Council MR/L501542/1Medical Research Council MR/N026004/1NIA NIH HHS RF1 AG058476Parkinson's UK G-0907Parkinson's UK H-1703Parkinson's UK K-1501
6 · The paper itself

Abstract

backgroundGenome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease.

methodsWe did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation.

findingsBetween Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16-36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10

interpretationThese data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data.

fundingThe National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources).

Indexed as

Databases, GeneticGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansParkinson DiseaseRisk Factors

Identifiers

PMID31701892
PMCPMC8422160
OpenAlexW2986932567

What OpenQuestion 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 OpenQuestion graph.