Evidence map›Paper›PMID 35732412›Full record

ArticleJournal of neurology, neurosurgery, and psychiatry2022

Genetics of validated Parkinson's disease subtypes in the Oxford Discovery and Tracking Parkinson's cohorts.

Michael Lawton, Manuela Mx Tan, Yoav Ben-Shlomo, Fahd Baig, Thomas Barber, Johannes C Klein, Samuel G Evetts, Stephanie Millin, Naveed Malek, Katherine Grosset and 8 more

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

Article in Journal of neurology, neurosurgery, and psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 18% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Classification and Genotype-Phenotype Relationships of GBA1 Variants: MDSGene Systematic Review.Movement disorders : official journal of the Movement Disorder Society · 2025
    Pooled it
  2. Article
  3. Article
  4. Refining the clinical diagnosis of Parkinson's disease.Parkinsonism & related disorders · 2024
    Review
  5. Article
  6. The epidemiology of Parkinson's disease.Lancet (London, England) · 2024
    Review
  7. Approaches to Early Parkinson's Disease Subtyping.Journal of Parkinson's disease · 2024
    Review
  8. Article
  9. Article
  10. 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

18 authors at 9 institutions in 1 country.

Michael LawtonPopulation Health Sciences, University of Bristol Medical School, Bristol, UK Michael.Lawton@bristol.ac.uk.ORCID http://orcid.org/0000-0002-3419-0354
Manuela Mx TanDepartment of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.ORCID http://orcid.org/0000-0001-5835-669X
Yoav Ben-ShlomoPopulation Health Sciences, University of Bristol Medical School, Bristol, UK.
Fahd BaigNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Thomas BarberNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Johannes C KleinNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-8553-2801
Samuel G EvettsNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Stephanie MillinOxford Parkinson's Disease Centre, University of Oxford, Oxford, UK.
Naveed MalekDepartment of Neurology, Queen's Hospital, Romford, Essex, UK.
Katherine GrossetDepartment of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital and University of Glasgow, Glasgow, UK.
Roger A BarkerCambridge Centre for Brain Repair, University of Cambridge, Cambridge, UK.
Nigel WilliamsPsychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
David J BurnFaculty of Medical Sciences, Newcastle University, Newcastle, UK.
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
Huw R MorrisDepartment of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.ORCID http://orcid.org/0000-0002-5473-3774
Nicholas WoodDepartment of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.
Donald G Grosset *Department of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital and University of Glasgow, Glasgow, UK.
Michele Tao-Ming Hu *Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0001-6382-5841
University of Oxford · GBKing's College London · GBQueen Elizabeth University Hospital · GBUniversity of Bristol · GBCardiff University · GBNewcastle University · GBQueen's Hospital · GBSt George's, University of London · GBUniversity of Cambridge · GB

Funding

Medical Research Council MR/L010305/1Parkinson's UK H-1703Parkinson's UK J-1101Wellcome Trust
6 · The paper itself

Abstract

objectivesTo explore the genetics of four Parkinson's disease (PD) subtypes that have been previously described in two large cohorts of patients with recently diagnosed PD. These subtypes came from a data-driven cluster analysis of phenotypic variables.

methodsWe looked at the frequency of genetic mutations in glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 against our subtypes. Then we calculated Genetic Risk Scores (GRS) for PD, multiple system atrophy, progressive supranuclear palsy, Lewy body dementia, and Alzheimer's disease. These GRSs were regressed against the probability of belonging to a subtype in the two independent cohorts and we calculated q-values as an adjustment for multiple testing across four subtypes. We also carried out a Genome-Wide Association Study (GWAS) of belonging to a subtype.

resultsA severe disease subtype had the highest rates of patients carrying GBA mutations while the mild disease subtype had the lowest rates (p=0.009). Using the GRS, we found a severe disease subtype had a reduced genetic risk of PD (p=0.004 and q=0.015). In our GWAS no individual variants met genome wide significance (<5×10e-8) although four variants require further follow-up, meeting a threshold of <1×10e-6.

conclusionsWe have found that four previously defined PD subtypes have different genetic determinants which will help to inform future studies looking at underlying disease mechanisms and pathogenesis in these different subtypes of disease.

Indexed as

GENETICSPARKINSON'S DISEASE

Identifiers

PMID35732412
PMCPMC9380504
OpenAlexW4283388357

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.