SynthesisNeurobiology of aging2021
Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson's disease.
Open access · hybridAbstract readMeta-Analysis
In one paragraph
Synthesis in Neurobiology of aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12citing papers in PubMed
1.5field-weighted citation impact, top 14% of its field
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Low-frequency genetic variants in GAK enhance Golgi function and protect against Parkinson's disease.medRxiv : the preprint server for health sciences · 2025Article
- Article
- LRRK2-Associated Parkinsonism With and WithoutmedRxiv : the preprint server for health sciences · 2024Article
- Loss of TDP-43 mediates severe neurotoxicity by suppressing PJA1 gene transcription in the monkey brain.Cellular and molecular life sciences : CMLS · 2024Article
- Immunological characterization and diagnostic models of RNA N6-methyladenosine regulators in Alzheimer's disease.Scientific reports · 2023Article
- LRRK2 and Parkinson's disease: from genetics to targeted therapy.Annals of clinical and translational neurology · 2023Review
- Genomewide Association Studies of LRRK2 Modifiers of Parkinson's Disease.Annals of neurology · 2021Article
- Role of SNAREs in Neurodegenerative Diseases.Cells · 2021Review
- Emerging genetic complexity and rare genetic variants in neurodegenerative brain diseases.Genome medicine · 2021Review
- Genetic and Environmental Factors Influence the Pleomorphy ofInternational journal of molecular sciences · 2021Review
- Variable Effects of PD-Risk Associated SNPs and Variants in Parkinsonism-Associated Genes on Disease Phenotype in a Community-Based Cohort.Frontiers in neurology · 2021Article
- Ten Years of the International Parkinson Disease Genomics Consortium: Progress and Next Steps.Journal of Parkinson's disease · 2020Article
Corrections and comments
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Authors and funding
34 authors at 19 institutions in 12 countries.
Emmeline E BrownDepartment of Clinical and Movement Neurosciences, Institute of Neurology, University College London, London, UK.
Cornelis BlauwendraatLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Joanne TrinhInstitute of Neurogenetics, University of Lübeck, Lübeck, Germany.
Mie RizigDepartment of Clinical and Movement Neurosciences, Institute of Neurology, University College London, London, UK.
Mike A NallsLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Data Tecnica International, Glen Echo, MD, USA.
Etienne LeveilleMontreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada.
Jennifer A RuskeyMontreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada.
Hallgeir JonvikDepartment of Clinical and Movement Neurosciences, Institute of Neurology, University College London, London, UK.
Manuela M X TanDepartment of Clinical and Movement Neurosciences, Institute of Neurology, University College London, London, UK.
Sara Bandres-CigaLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain.
Sharon Hassin-BaerSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Neurology, Sheba Medical Center, Tel HaShomer, Israel; Movement Disorders Institute, Sheba Medical Center, Tel HaShomer, Israel.
Kathrin BrockmannHertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, University Clinic Tu¨bingen, Tu¨bingen, Germany.
Jon InfanteService of Neurology, University Hospital "Marqués de Valdecilla (IDIVAL)", University of Cantabria; "Centro de Investigación Biomédica en Red de Enfermedades, Neurodegenerativas (CIBERNED)", Santander, Spain.
Eduardo TolosaLaboratory of Parkinson Disease & Other Neurodegenerative Movement Disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) - Hospital Clínic de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED: CB06/05/0018-ISCIII), Barcelona, Spain.
Mario EzquerraLaboratory of Parkinson Disease & Other Neurodegenerative Movement Disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) - Hospital Clínic de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED: CB06/05/0018-ISCIII), Barcelona, Spain.
Sawssan Ben RomdhanResearch Unit in Neurogenetics, Clinical Investigation Center (CIC) at the CHU Habib Bourguiba, Sfax, Tunisia.
Mustapha BenmahdjoubFrantz Fanon Hospital, CHU Blida, Blida, Algeria.
Mohamed ArezkiFrantz Fanon Hospital, CHU Blida, Blida, Algeria.
Chokri MhiriFrantz Fanon Hospital, CHU Blida, Blida, Algeria.
John HardyDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK; UK Dementia Research Institute at UCL and Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK; Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, 1 Wakefield Street, London WC1N 1PJ, UK; UCL Movement Disorders Centre, University College London, London, UK; Institute for Advanced Study, The Hong Kong University of Science and Technology, Hong Kong SAR, China.
Andrew B SingletonLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Roy N AlcalayDepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
Thomas GasserDepartment for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tu¨bingen, Tu¨bingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Tu¨bingen, Germany.
Donald G GrossetDepartment of Neurology, Institute of Neurological Sciences, Queen Elizabeth University Hospital, Glasgow, UK; Institute of Neuroscience & Psychology, University of Glasgow, Glasgow, UK.
Nigel M WilliamsDivision of Psychological Medicine & Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff, UK.
Alan PittmanDepartment of Clinical Genetics, St George's, University of London, London, UK.
Ziv Gan-OrMontreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
Ruben Fernandez-SantiagoLaboratory of Parkinson Disease & Other Neurodegenerative Movement Disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) - Hospital Clínic de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED: CB06/05/0018-ISCIII), Barcelona, Spain.
Alexis BriceResearch Unit U1127 at INSERM, Research Unit UMR 7225 at the French National Centre for Scientific Research (CNRS) Research Unit UMR_1127 at Sorbonne Université, Institutet du Cerveau et de la Moëlle épinière (ICM), Paris, France.
Suzanne LesageResearch Unit U1127 at INSERM, Research Unit UMR 7225 at the French National Centre for Scientific Research (CNRS) Research Unit UMR_1127 at Sorbonne Université, Institutet du Cerveau et de la Moëlle épinière (ICM), Paris, France.
Matthew FarrerDepartment of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Nicholas WoodDepartment of Clinical and Movement Neurosciences, Institute of Neurology, University College London, London, UK.
Huw R MorrisDepartment of Clinical and Movement Neurosciences, Institute of Neurology, University College London, London, UK. Electronic address: h.morris@ucl.ac.uk.
International Parkinson Disease Genomics Consortium (IPDGC)
University College London · GBMcGill University · CANational Institutes of Health · USBiomedical Research Networking Center on Neurodegenerative Diseases · ESThorax Foundation · GRUniversity of Blida · DZUniversity of Tübingen · DEAllen Institute for Brain Science · USAssociazione Frantz Fanon · ITCardiff University · GBColumbia University · USHopital Universitaire Habib Bourguiba · TNInstitut du Cerveau · FRNational Institute on Aging · USQueen Elizabeth University Hospital · GBTechnical University of Applied Sciences Lübeck · DETel Aviv University · ILUniversidad de Londres · MXUniversity of British Columbia · CA
Funding
Genome wide SNP analysis in Parkinson's diseaseZIAAG000949 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW · 2009 to 2024
$12.6MAssessment of Candidate Loci in Neurological diseasesZIAAG000957 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW · 2009 to 2024
$12.2MDepartment of HealthMedical 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/N026004/1Parkinson's UK G-0907Parkinson's UK K-1501Wellcome TrustWellcome Trust 202903/Z/16/Z
Abstract
The LRRK2 gene has rare (p.G2019S) and common risk variants for Parkinson's disease (PD). DNM3 has previously been reported as a genetic modifier of the age at onset in PD patients carrying the LRRK2 p.G2019S mutation. We analyzed this effect in a new cohort of LRRK2 p.G2019S heterozygotes (n = 724) and meta-analyzed our data with previously published data (n = 754). VAMP4 is in close proximity to DNM3, and was associated with PD in a recent study, so it is possible that variants in this gene may be important. We also analyzed the effect of VAMP4 rs11578699 on LRRK2 penetrance. Our analysis of DNM3 in previously unpublished data does not show an effect on age at onset in LRRK2 p.G2019S carriers; however, the inter-study heterogeneity may indicate ethnic or population-specific effects of DNM3. There was no evidence for linkage disequilibrium between DNM3 and VAMP4. Analysis of sporadic patients stratified by the risk variant LRRK2 rs10878226 indicates a possible interaction between common variation in LRRK2 and VAMP4 in disease risk.
Indexed as
Genetic Association StudiesAgedAge of OnsetCohort StudiesDynamin IIIEpistasis, GeneticFemaleGenetic Predisposition to DiseaseGenetic VariationHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Linkage DisequilibriumMaleMiddle AgedParkinson DiseaseRiskDynamin IIILeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanR-SNARE ProteinsVAMP4 protein, humanGenetic modifiersLeucine-rich repeat kinase 2ParkinsonismParkinson’s disease
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