Evidence map›Paper›PMID 38849413›Full record

ArticleNPJ Parkinson's disease2024

Genome-wide determinants of mortality and motor progression in Parkinson's disease.

Manuela M X Tan, Michael A Lawton, Miriam I Pollard, Emmeline Brown, Raquel Real, Alejandro Martinez Carrasco, Samir Bekadar, Edwin Jabbari, Regina H Reynolds, Hirotaka Iwaki and 30 more

Abstract read
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In one paragraph

Article in NPJ Parkinson's disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
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

16 citing papers in PubMed.

  1. Journal of Parkinson's disease · 2026
    Review
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Genetic drivers of progression in Alzheimer's disease are distinct from disease risk.medRxiv : the preprint server for health sciences · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. 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

40 authors.

Manuela M X TanDepartment of Neurology, Oslo University Hospital, Oslo, Norway. manuela.tan@medisin.uio.no.ORCID http://orcid.org/0000-0001-5835-669X
Michael A LawtonPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID http://orcid.org/0000-0002-3419-0354
Miriam I PollardDepartment of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.
Emmeline BrownDepartment of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.
Raquel RealDepartment of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.ORCID http://orcid.org/0000-0001-8117-742X
Alejandro Martinez CarrascoDepartment of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.ORCID http://orcid.org/0000-0001-6191-1703
Samir BekadarSorbonne University, Paris Brain Institute - ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, Departement of Neurology, Hôpital Pitié-Salpêtrière, Paris, France.
Edwin JabbariDepartment of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.ORCID http://orcid.org/0000-0001-6844-882X
Regina H ReynoldsAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.ORCID http://orcid.org/0000-0001-6470-7919
Hirotaka IwakiLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8982-7885
Cornelis BlauwendraatLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-9358-8111
Sofia KanavouPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Leon HubbardInstitute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Naveed MalekDepartment of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK.
Katherine A GrossetDepartment of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK.
Nin BajajClinical Neurosciences, University of Nottingham, Nottingham, UK.
Roger A BarkerAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.ORCID http://orcid.org/0000-0001-8843-7730
David J BurnFaculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Catherine BresnerInstitute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.ORCID http://orcid.org/0000-0003-2673-9762
Thomas FoltynieDepartment of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.ORCID http://orcid.org/0000-0003-0752-1813
Nicholas W WoodDepartment of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.ORCID http://orcid.org/0000-0002-9500-3348
Caroline H Williams-GrayJohn Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-2648-9743
Ole A AndreassenNORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.ORCID http://orcid.org/0000-0002-4461-3568
Mathias ToftDepartment of Neurology, Oslo University Hospital, Oslo, Norway.
Alexis ElbazParis-Saclay University, UVSQ, Inserm, Gustave Roussy, "Exposome and Heredity" team, CESP, 94807, Villejuif, France.ORCID http://orcid.org/0000-0001-9724-5490
Fanny ArtaudParis-Saclay University, UVSQ, Inserm, Gustave Roussy, "Exposome and Heredity" team, CESP, 94807, Villejuif, France.
Alexis BriceSorbonne University, Paris Brain Institute - ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, Departement of Neurology, Hôpital Pitié-Salpêtrière, Paris, France.
Jean-Christophe CorvolSorbonne University, Paris Brain Institute - ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, Departement of Neurology, Hôpital Pitié-Salpêtrière, Paris, France.ORCID http://orcid.org/0000-0001-7325-0199
Jan AaslyDepartment of Neurology, St. Olavs Hospital, Trondheim, Norway.
Matthew J FarrerDepartment of Neurology, University of Florida, Gainesville, FL, USA.ORCID http://orcid.org/0000-0003-1159-5321
Michael A NallsLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-0319-4325
Andrew B SingletonLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Nigel M WilliamsInstitute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.ORCID http://orcid.org/0000-0003-1177-6931
Yoav Ben-ShlomoPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
John HardyUCL Movement Disorders Centre, University College London, London, UK.ORCID http://orcid.org/0000-0002-3122-0423
Michele T M HuNuffield Department of Clinical Neurosciences, Division of Clinical Neurology, University of Oxford, Oxford, UK.
Donald G GrossetSchool of Neuroscience and Psychology, University of Glasgow, Glasgow, UK.
Maryam ShoaiAligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.ORCID http://orcid.org/0000-0003-2499-8533
Lasse PihlstrømDepartment of Neurology, Oslo University Hospital, Oslo, Norway.ORCID http://orcid.org/0000-0002-7635-8645
Huw R MorrisDepartment of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK. h.morris@ucl.ac.uk.ORCID http://orcid.org/0000-0002-5473-3774

Funding

Harmonized Data-Derived Resources for the Alzheimer's Disease and Related Dementias CommunityZIAAG000534 · NIA · NATIONAL INSTITUTE ON AGING · PI COOKSON, MARK · 2019 to 2025
$85.1M
Genome wide SNP analysis in Parkinson's diseaseZIAAG000949 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW · 2009 to 2024
$12.6M
Intramural NIH HHS ZIA AG000949Medical Research Council MC_PC_17230Medical Research Council MR/W029235/1Parkinson's UK H-1703RCUK | Medical Research Council (MRC) MR/R007446/1Wellcome Trust
6 · The paper itself

Abstract

There are 90 independent genome-wide significant genetic risk variants for Parkinson's disease (PD) but currently only five nominated loci for PD progression. The biology of PD progression is likely to be of central importance in defining mechanisms that can be used to develop new treatments. We studied 6766 PD patients, over 15,340 visits with a mean follow-up of between 4.2 and 15.7 years and carried out genome-wide survival studies for time to a motor progression endpoint, defined by reaching Hoehn and Yahr stage 3 or greater, and death (mortality). There was a robust effect of the APOE ε4 allele on mortality in PD. We also identified a locus within the TBXAS1 gene encoding thromboxane A synthase 1 associated with mortality in PD. We also report 4 independent loci associated with motor progression in or near MORN1, ASNS, PDE5A, and XPO1. Only the non-Gaucher disease causing GBA1 PD risk variant E326K, of the known PD risk variants, was associated with mortality in PD. Further work is needed to understand the links between these genomic variants and the underlying disease biology. However, these may represent new candidates for disease modification in PD.

Identifiers

PMID38849413
PMCPMC11161485

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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.