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Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson's disease.

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dc.contributor.authorBrown, Emmeline E
dc.contributor.authorBlauwendraat, Cornelis
dc.contributor.authorTrinh, Joanne
dc.contributor.authorRizig, Mie
dc.contributor.authorNalls, Mike A
dc.contributor.authorLeveille, Etienne
dc.contributor.authorRuskey, Jennifer A
dc.contributor.authorJonvik, Hallgeir
dc.contributor.authorTan, Manuela M X
dc.contributor.authorBandres-Ciga, Sara
dc.contributor.authorHassin-Baer, Sharon
dc.contributor.authorBrockmann, Kathrin
dc.contributor.authorInfante, Jon
dc.contributor.authorTolosa, Eduardo
dc.contributor.authorEzquerra, Mario
dc.contributor.authorBen Romdhan, Sawssan
dc.contributor.authorBenmahdjoub, Mustapha
dc.contributor.authorArezki, Mohamed
dc.contributor.authorMhiri, Chokri
dc.contributor.authorHardy, John
dc.contributor.authorSingleton, Andrew B
dc.contributor.authorAlcalay, Roy N
dc.contributor.authorGasser, Thomas
dc.contributor.authorGrosset, Donald G
dc.contributor.authorWilliams, Nigel M
dc.contributor.authorPittman, Alan
dc.contributor.authorGan-Or, Ziv
dc.contributor.authorFernandez-Santiago, Ruben
dc.contributor.authorBrice, Alexis
dc.contributor.authorLesage, Suzanne
dc.contributor.authorFarrer, Matthew
dc.contributor.authorWood, Nicholas
dc.contributor.authorMorris, Huw R
dc.contributor.funderParkinson's UK
dc.contributor.funderMedical Research Council (MRC)
dc.contributor.funderAlzheimer's Society and Alzheimer’s Research UK,
dc.contributor.groupInternational Parkinson Disease Genomics Consortium (IPDGC)
dc.date.accessioned2023-02-09T09:39:43Z
dc.date.available2023-02-09T09:39:43Z
dc.date.issued2020-07-03
dc.description.abstractThe 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 Our analysis of DNM3 in previously unpublished data does not show an effect on age at onset in LRRK2 p.G2019S carriers; however, the inter-study heterogeneity may indicate ethnic or population-specific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.
dc.description.sponsorshipThe authors would like to thank all of the Parkinson’s disease patients and unaffected relatives who donated their time and biological samples to be part of this study. The authors would also like to thank all members of the International Parkinson Disease Genomics Consortium (IPDGC). For a complete overview of IPDGC members, acknowledgments, and funding, please see http://pdgenetics.org/partners . This work was supported by Parkinson's UK (grant numbers: J-1101, H-1703), University College London (UCL), the NIHR Rare Diseases Translational Research Consortium, the Medical Research Council (MRC) (award number MR/N026004/1), the Intramural Research Programs of the National Institute of Neurological Disorders, and Stroke (NINDS) and the National Institute on Aging (NIA), UK Dementia Research Institute which receives its funding from DRI Ltd (funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK), Alzheimer's Society and Alzheimer’s Research UK, Wellcome Trust Hardy (award number 202903/Z/16/Z), Dolby Family Fund, National Institute for Health Research University College London Hospitals Biomedical Research Centre, BRCNIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London. Funding sources had no involvement in study design, collection, analysis and interpretation of data.
dc.description.versionSi
dc.identifier.citationBrown EE, Blauwendraat C, Trinh J, Rizig M, Nalls MA, Leveille E, et al. Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson's disease. Neurobiol Aging. 2021 Jan;97:148.e17-148.e24.
dc.identifier.doi10.1016/j.neurobiolaging.2020.07.002
dc.identifier.essn1558-1497
dc.identifier.pmcPMC7762821
dc.identifier.pmid32873436
dc.identifier.unpaywallURLhttps://doi.org/10.1016/j.neurobiolaging.2020.07.002
dc.identifier.urihttp://hdl.handle.net/10668/16190
dc.journal.titleNeurobiology of aging
dc.journal.titleabbreviationNeurobiol Aging
dc.language.isoen
dc.organizationInstituto de Investigación Biosanitaria de Granada (ibs.GRANADA)
dc.page.number148.e17-148.e24
dc.publisherElsevier Inc.
dc.pubmedtypeJournal Article
dc.pubmedtypeMeta-Analysis
dc.pubmedtypeResearch Support, N.I.H., Intramural
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.relation.projectIDJ-1101
dc.relation.projectIDH-1703
dc.relation.projectIDMR/N026004/1
dc.relation.projectID202903/Z/16/Z
dc.relation.publisherversionhttps://linkinghub.elsevier.com/retrieve/pii/S0197-4580(20)30218-9
dc.rightsAttribution 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectGenetic modifiers
dc.subjectLeucine-rich repeat kinase 2
dc.subjectParkinsonism
dc.subjectParkinson’s disease
dc.subject.decsAnciano
dc.subject.decsDesequilibrio de ligamiento
dc.subject.decsDinamina III
dc.subject.decsEdad de inicio
dc.subject.decsEnfermedad de Parkinson
dc.subject.decsEpistasis genética
dc.subject.decsEstudios de asociación genética
dc.subject.decsEstudios de cohortes
dc.subject.decsPredisposición genética a la enfermedad
dc.subject.decsProteína 2 quinasa serina-treonina rica en repeticiones de leucina
dc.subject.decsProteínas R-SNARE
dc.subject.decsRiesgo
dc.subject.decsVariación genética
dc.subject.meshAge of Onset
dc.subject.meshAged
dc.subject.meshCohort Studies
dc.subject.meshDynamin III
dc.subject.meshEpistasis, Genetic
dc.subject.meshFemale
dc.subject.meshGenetic Association Studies
dc.subject.meshGenetic Predisposition to Disease
dc.subject.meshGenetic Variation
dc.subject.meshHumans
dc.subject.meshLeucine-Rich Repeat Serine-Threonine Protein Kinase-2
dc.subject.meshLinkage Disequilibrium
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshParkinson Disease
dc.subject.meshR-SNARE Proteins
dc.subject.meshRisk
dc.titleAnalysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson's disease.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number97
dspace.entity.typePublication

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