ArticleNature genetics2021
Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson's disease.
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In one paragraph
Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 2 pooled it
18.7field-weighted citation impact, top 1% of its field
What it found
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The trial behind it
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Who cites it
84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 137 citations in OpenAlex.
- Interrogating DNA methylation associated with Lewy body pathology in a cross brain-region and multi-cohort study.Nature communications · 2026Pooled it
- Association between the LRP1B and APOE loci and the development of Parkinson's disease dementia.Brain : a journal of neurology · 2023Pooled it
- Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.Nature communications · 2026Article
- The emerging role of circular RNAs in neurodegenerative diseases and viral infections.Journal of neurovirology · 2026Review
- Charting the human-specific properties of gene expression networks in the infant prefrontal cortex.Science advances · 2026Article
- Multi-locus genetic dosage shapes cognitive disease progression in Parkinson's patients: 15-year meta-analysis of 24 cohorts.NPJ Parkinson's disease · 2026Article
- Single-cell eQTL mapping reveals convergent glial-neuronal risk architecture in Parkinson's disease.bioRxiv : the preprint server for biology · 2026Article
- Comparative Single-Cell Transcriptomic Atlas Reveals the Genetic Regulation of Reproductive Traits.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genetic risk loci for Parkinson's disease and dementia in a large-scale population-based Taiwanese cohort (TPMI).The Lancet regional health. Western Pacific · 2026Article
- Characteristics and mechanisms of cognitive impairment in Parkinson disease.Nature reviews. Neurology · 2026Review
- Genetics to Improve Outcomes in Schizophrenia (GENios): A within-case molecular genetic study protocol.PloS one · 2026Article
- Intracellular trafficking SNARE protein, syntaxin-6, modifies prion cellular phenotypes and risk of disease development in vivo.Acta neuropathologica · 2025Article
- Progression to Parkinson's dementia is not modulated by genetic risk variants for Alzheimer's or Parkinson's disease.Journal of Parkinson's disease · 2025Article
- Limited overlap between genetic effects on disease susceptibility and disease survival.Nature genetics · 2025Article
- Tackling a disease on a global scale, the Global Parkinson's Genetics Program, GP2: A new generation of opportunities.American journal of human genetics · 2025Review
- Genetic Analysis of the X Chromosome Associates Loci with Progression of Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Multi-omics machine learning classifier and blood transcriptomic signature of Parkinson's disease.Research square · 2025Article
- FUS Mislocalization Rewires a Cortical Gene Network to Drive Cognitive and Behavioral Impairment in ALS.medRxiv : the preprint server for health sciences · 2025Article
- Review
- Predicting dementia in people with Parkinson's disease.NPJ Parkinson's disease · 2025Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
40 authors at 19 institutions in 9 countries.
Ganqiang LiuCenter for Advanced Parkinson Research, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1921-9542
Jiajie PengCenter for Advanced Parkinson Research, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Zhixiang LiaoCenter for Advanced Parkinson Research, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Joseph J LocascioCenter for Advanced Parkinson Research, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Jean-Christophe CorvolSorbonne Université, Paris Brain Institute - Institut du Cerveau - ICM, Institut National de Santé et en Recherche Médicale, Centre National de Recherche Scientifique, Assistance Publique Hôpitaux de Paris, Département de Neurologie et de Génétique, Centre d'Investigation Clinique Neurosciences, Hôpital Pitié-Salpêtrière, Paris, France.
Frank ZhuCenter for Advanced Parkinson Research, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Xianjun DongCenter for Advanced Parkinson Research, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8052-9320
Jodi Maple-GrødemThe Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.ORCID http://orcid.org/0000-0001-7142-0078
Meghan C CampbellDepartments of Neurology and Radiology, Washington University School of Medicine, St. Louis, MO, USA.
Alexis ElbazParis-Saclay University, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Inserm, Gustave Roussy, 'Exposome and heredity' team, Centre de researche en épidémiologie et santé des populations (CESP), Villejuif, France.ORCID http://orcid.org/0000-0001-9724-5490
Suzanne LesageSorbonne Université, Paris Brain Institute - Institut du Cerveau - ICM, Institut National de Santé et en Recherche Médicale, Centre National de Recherche Scientifique, Assistance Publique Hôpitaux de Paris, Département de Neurologie et de Génétique, Centre d'Investigation Clinique Neurosciences, Hôpital Pitié-Salpêtrière, Paris, France.
Alexis BriceSorbonne Université, Paris Brain Institute - Institut du Cerveau - ICM, Institut National de Santé et en Recherche Médicale, Centre National de Recherche Scientifique, Assistance Publique Hôpitaux de Paris, Département de Neurologie et de Génétique, Centre d'Investigation Clinique Neurosciences, Hôpital Pitié-Salpêtrière, Paris, France.
Graziella MangoneSorbonne Université, Paris Brain Institute - Institut du Cerveau - ICM, Institut National de Santé et en Recherche Médicale, Centre National de Recherche Scientifique, Assistance Publique Hôpitaux de Paris, Département de Neurologie et de Génétique, Centre d'Investigation Clinique Neurosciences, Hôpital Pitié-Salpêtrière, Paris, France.
John H GrowdonDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Albert Y HungDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3658-571X
Michael A SchwarzschildDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Michael T HayesCenter for Advanced Parkinson Research, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Anne-Marie WillsDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Todd M HerringtonDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Bernard RavinaPraxis Precision Medicines, Cambridge, MA, USA.
Ira ShoulsonDepartment of Neurology, Center for Health + Technology, University of Rochester, Rochester, NY, USA.
Pille TabaDepartment of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
Sulev KõksCentre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth, Western Australia, Australia.ORCID http://orcid.org/0000-0001-6087-6643
Thomas G BeachBanner Sun Health Research Institute, Sun City, AZ, USA.
Florence Cormier-DequaireSorbonne Université, Paris Brain Institute - Institut du Cerveau - ICM, Institut National de Santé et en Recherche Médicale, Centre National de Recherche Scientifique, Assistance Publique Hôpitaux de Paris, Département de Neurologie et de Génétique, Centre d'Investigation Clinique Neurosciences, Hôpital Pitié-Salpêtrière, Paris, France.
Guido AlvesThe Norwegian Centre for Movement Disorders, Stavanger University Hospital, Stavanger, Norway.ORCID http://orcid.org/0000-0003-0630-2870
Ole-Bjørn TysnesDepartment of Neurology, Haukeland University Hospital, Bergen, Norway.
Joel S PerlmutterDepartments of Neurology and Radiology, Washington University School of Medicine, St. Louis, MO, USA.
Peter HeutinkGerman Center for Neurodegenerative diseases (DZNE), Tübingen, Germany.ORCID http://orcid.org/0000-0001-5218-1737
Sami S AmrTranslational Genomics Core of Partners HealthCare Personalized Medicine, Cambridge, MA, USA.
Jacobus J van HiltenDepartment of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
Meike KastenInstitute of Neurogenetics, University of Lübeck, University Hospital of Schleswig-Holstein, Lübeck, Germany.
Brit MollenhauerDepartment of Neurology, University Medical Center Göttingen, Göttingen, Germany.
Claudia TrenkwalderParacelsus-Elena-Klinik, Kassel, Germany.
Christine KleinInstitute of Neurogenetics, University of Lübeck, University Hospital of Schleswig-Holstein, Lübeck, Germany.
Roger A BarkerJohn Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Caroline H Williams-GrayJohn Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Johan MarinusDepartment of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
International Genetics of Parkinson Disease Progression (IGPP) Consortium
Clemens R ScherzerCenter for Advanced Parkinson Research, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA. cscherzer@rics.bwh.harvard.edu.ORCID http://orcid.org/0000-0002-0567-9193
Brigham and Women's Hospital · USHarvard University · USSorbonne Université · FRLeiden University Medical Center · NLStavanger University Hospital · NOUniversitätsmedizin Göttingen · DEUniversity of Lübeck · DEWashington University in St. Louis · USBanner Sun Health Research Institute · USGerman Center for Neurodegenerative Diseases · DEHaukeland University Hospital · NOInserm · FRMass General Brigham · USMurdoch University · AUPraxis (United States) · USUniversity of Cambridge · GBUniversity of Rochester · USUniversity of Tartu · EEWellcome/MRC Cambridge Stem Cell Institute · GB
Funding
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8MNINDS Biomarker RepositoryU24NS095871 · NINDS · INDIANA UNIVERSITY INDIANAPOLIS · PI TATIANA M. FOROUD · 2015 to 2026
$18.3MGenome-Wide Prediction of Dementia in Parkinson's DiseaseR01NS115144 · NINDS · YALE UNIVERSITY · PI SCHERZER, CLEMENS R · 2019 to 2025
$4.4MGBA pathway markers for Lewy body dementiasU01NS100603 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI SCHERZER, CLEMENS R · 2016 to 2020
$2.9MParkinson Disease: Predicting the FutureU01NS095736 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI SCHERZER, CLEMENS R · 2016 to 2018
$2.1MUsing phasic stimulation to explore the subthalamic nucleus - cortical decision-making network in Parkinson's diseaseK23NS099380 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI HERRINGTON, TODD · 2017 to 2021
$1.0MMedical Research Council MC_PC_17230Medical Research Council MR/R007446/1NIA NIH HHS U24 AG021886NINDS NIH HHS K23 NS099380NINDS NIH HHS R01 NS115144NINDS NIH HHS U01 NS095736NINDS NIH HHS U01 NS100603NINDS NIH HHS U24 NS095871Wellcome Trust
Abstract
A key driver of patients' well-being and clinical trials for Parkinson's disease (PD) is the course that the disease takes over time (progression and prognosis). To assess how genetic variation influences the progression of PD over time to dementia, a major determinant for quality of life, we performed a longitudinal genome-wide survival study of 11.2 million variants in 3,821 patients with PD over 31,053 visits. We discover RIMS2 as a progression locus and confirm this in a replicate population (hazard ratio (HR) = 4.77, P = 2.78 × 10
Indexed as
CognitionDisease ProgressionGenetic LociGenome-Wide Association StudyApolipoprotein E4Cognition DisordersGenetic Predisposition to DiseaseGlucosylceramidaseHumansLongitudinal StudiesMultifactorial InheritanceMutationParkinson DiseaseProportional Hazards ModelsRisk FactorsSurvival AnalysisApolipoprotein E4GBA protein, humanGlucosylceramidase
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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.