Evidence map›Paper›PMID 33341150›Full record

ArticleThe Lancet. Neurology2021

Genetic determinants of survival in progressive supranuclear palsy: a genome-wide association study.

Edwin Jabbari, Shunsuke Koga, Rebecca R Valentino, Regina H Reynolds, Raffaele Ferrari, Manuela M X Tan, James B Rowe, Clifton L Dalgard, Sonja W Scholz, Dennis W Dickson and 9 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06647641 (The CurePSP Genetics Program), which is not on this map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 3% 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.

NCT06647641 recruitingnot on this mapstarted 2024, after this paper: background citation

The CurePSP Genetics Program

TypeobservationalSponsorMassachusetts General HospitalRan2024 to 2030Enrolled1,000ConditionsPSP, PSP - Progressive Supranuclear Palsy, Corticobasal Syndrome, Corticobasal Syndrome(CBS)ArmsWhole genome sequencing will be performed at the NIH
3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.

  1. Coding and Noncoding Variation in LRRK2 and Parkinson's Disease Risk.Movement disorders : official journal of the Movement Disorder Society · 2022
    Pooled it
  2. Article
  3. Biomarkers of Leucine-Rich Repeat Kinase 2 (LRRK2) and Lysosomal Dysfunction in Progressive Supranuclear Palsy.Movement disorders : official journal of the Movement Disorder Society · 2026
    Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Genetic drivers of progression in Alzheimer's disease are distinct from disease risk.medRxiv : the preprint server for health sciences · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. The RAB32 p.Ser71Arg Variant in Parkinsonisms: Insights from a Large Italian Cohort.Movement disorders : official journal of the Movement Disorder Society · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 9 institutions in 5 countries.

Edwin JabbariDepartment of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK; Movement Disorders Centre, University College London Queen Square Institute of Neurology, London, UK. Electronic address: e.jabbari@ucl.ac.uk.
Shunsuke KogaDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Rebecca R ValentinoDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Regina H ReynoldsDepartment of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK; Great Ormond Street Institute of Child Health, Genetics and Genomic Medicine, University College London, London, UK.
Raffaele FerrariDepartment of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK.
Manuela M X TanDepartment of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK; Movement Disorders Centre, University College London Queen Square Institute of Neurology, London, UK.
James B RoweDepartment of Clinical Neurosciences, University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Clifton L DalgardDepartment of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Sonja W ScholzDepartment of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA; Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Thomas T WarnerReta Lila Weston Institute, University College London Queen Square Institute of Neurology, London, UK; Queen Square Brain Bank for Neurological Disorders, University College London Queen Square Institute of Neurology, London, UK.
Tamas ReveszReta Lila Weston Institute, University College London Queen Square Institute of Neurology, London, UK; Queen Square Brain Bank for Neurological Disorders, University College London Queen Square Institute of Neurology, London, UK.
Günter U HöglingerGerman Center for Neurodegenerative Diseases, Munich, Germany; Department of Neurology, Hannover Medical School, Hannover, Germany.
Owen A RossDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Mina RytenDepartment of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK; Great Ormond Street Institute of Child Health, Genetics and Genomic Medicine, University College London, London, UK.
John HardyDepartment of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK; Reta Lila Weston Institute, University College London Queen Square Institute of Neurology, London, UK; Dementia Research Institute at University College London, University College London Queen Square Institute of Neurology, London, UK; Institute for Advanced Study, The Hong Kong University of Science and Technology, Hong Kong Special Administrative Region, China.
Maryam ShoaiDepartment of Neurodegenerative Disease, University College London Queen Square Institute of Neurology, London, UK.
Huw R MorrisDepartment of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London, UK; Movement Disorders Centre, University College London Queen Square Institute of Neurology, London, UK. Electronic address: h.morris@ucl.ac.uk.
PSP Genetics Group
National Hospital for Neurology and Neurosurgery · GBQueen Mary University of London · GBMayo Clinic in Florida · USGreat Ormond Street Hospital · GBGerman Center for Neurodegenerative Diseases · DENational Institutes of Health · USUniformed Services University of the Health Sciences · USUniversity of Cambridge · GBUniversity of London · GB

Funding

'T V ASSESSMENT - MEMORY DISORDERED PATIENTS'P50AG005146 · NIA · JOHNS HOPKINS UNIVERSITY · PI LYKETSOS, CONSTANTINE G · 1985 to 2019
$37.6M
Genetic characterization of atypical parkinsonismZIANS003154 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI SCHOLZ, SONJA · 2016 to 2025
$15.4M
Project 2: Identifying genes and Pathways that impact Tau Toxicity in FTDU54NS100693 · NINDS · MAYO CLINIC JACKSONVILLE · PI DICKSON, DENNIS WILLIAM · 2016 to 2020
$6.2M
Impact of coding and non-coding variation in progressive supranuclear palsyUG3NS104095 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DICKSON, DENNIS WILLIAM, GESCHWIND, DANIEL H · 2017 to 2019
$3.6M
Impact of coding and non-coding variation in progressive supranuclear palsyUH3NS104095 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DICKSON, DENNIS WILLIAM, GESCHWIND, DANIEL H · 2020 to 2021
$2.5M
Multi-modal magnetic resonance imaging in progressive supranuclear palsy (PSP)K23AG059891 · NIA · JOHNS HOPKINS UNIVERSITY · PI PANTELYAT, ALEXANDER Y. · 2018 to 2022
$968k
Genome sequencing of Lewy Body Dementia and Frontotemporal Dementia: a public resource for the study of Alzheimers disease and related dementiasZIAAG000935 · NIA · NATIONAL INSTITUTE ON AGING · PI TRAYNOR, BRYAN · 2017 to 2025
$771k
Department of HealthIntramural NIH HHS ZIA AG000935Intramural NIH HHS ZIA NS003154Medical Research Council 548211Medical Research Council G0400074Medical Research Council G0502157Medical Research Council G0802462Medical Research Council G0900652Medical Research Council G1100540Medical Research Council MC_EX_MR/N50192X/1Medical Research Council MC_U105597119Medical Research Council MC_UU_00005/12Medical Research Council MR/L016397/1Medical Research Council MR/L023784/1Medical Research Council MR/L501542/1Medical Research Council MR/M024962/1Medical Research Council MR/N008324/1Medical Research Council MR/N026004/1Medical Research Council MR/S000992/1Medical Research Council MR/T018569/1NIA NIH HHS K23 AG059891NIA NIH HHS L30 AG064696NIA NIH HHS P50 AG005146NINDS NIH HHS U54 NS100693NINDS NIH HHS UG3 NS104095NINDS NIH HHS UH3 NS104095Parkinson's UK H-1703Parkinson's UK J-0901Wellcome TrustWellcome Trust 103838Wellcome Trust 202903/Z/16/Z
6 · The paper itself

Abstract

backgroundThe genetic basis of variation in the progression of primary tauopathies has not been determined. We aimed to identify genetic determinants of survival in progressive supranuclear palsy (PSP).

methodsIn stage one of this two stage genome-wide association study (GWAS), we included individuals with PSP, diagnosed according to pathological and clinical criteria, from two separate cohorts: the 2011 PSP GWAS cohort, from brain banks based at the Mayo Clinic (Jacksonville, FL, USA) and in Munich (Germany), and the University College London PSP cohort, from brain banks and the PROSPECT study, a UK-wide longitudinal study of patients with atypical parkinsonian syndromes. Individuals were included if they had clinical data available on sex, age at motor symptom onset, disease duration (from motor symptom onset to death or to the date of censoring, Dec 1, 2019, if individuals were alive), and PSP phenotype (with reference to the 2017 Movement Disorder Society criteria). Genotype data were used to do a survival GWAS using a Cox proportional hazards model. In stage two, data from additional individuals from the Mayo Clinic brain bank, which were obtained after the 2011 PSP GWAS, were used for a pooled analysis. We assessed the expression quantitative trait loci (eQTL) profile of variants that passed genome-wide significance in our GWAS using the Functional Mapping and Annotation of GWAS platform, and did colocalisation analyses using the eQTLGen and PsychENCODE datasets.

findingsData were collected and analysed between Aug 1, 2016, and Feb 1, 2020. Data were available for 1001 individuals of white European ancestry with PSP in stage one. We found a genome-wide significant association with survival at chromosome 12 (lead single nucleotide polymorphism rs2242367, p=7·5 × 10

interpretationGenetic variation at the LRRK2 locus was associated with survival in PSP. The mechanism of this association might be through a lncRNA-regulated effect on LRRK2 expression because LINC02555 has previously been shown to regulate LRRK2 expression. LRRK2 has been associated with sporadic and familial forms of Parkinson's disease, and our finding suggests a genetic overlap with PSP. Further functional studies will be important to assess the potential of LRRK2 modulation as a disease-modifying therapy for PSP and related tauopathies.

fundingPSP Association, CBD Solutions, Medical Research Council (UK).

Indexed as

Genome-Wide Association StudyAdultAgedAge of OnsetChromosomes, Human, Pair 12Databases, GeneticFemaleGenetic Predisposition to DiseaseGenetic VariationHumansKaplan-Meier EstimateLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Linkage DisequilibriumMaleMiddle AgedPolymorphism, Single NucleotideLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanRNA, Long Noncoding

Identifiers

PMID33341150
PMCPMC7116626
OpenAlexW3112289740

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Registered trials

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.