Brown, Emmeline EBlauwendraat, CornelisTrinh, JoanneRizig, MieNalls, Mike ALeveille, EtienneRuskey, Jennifer AJonvik, HallgeirTan, Manuela M XBandres-Ciga, SaraHassin-Baer, SharonBrockmann, KathrinInfante, JonTolosa, EduardoEzquerra, MarioBen Romdhan, SawssanBenmahdjoub, MustaphaArezki, MohamedMhiri, ChokriHardy, JohnSingleton, Andrew BAlcalay, Roy NGasser, ThomasGrosset, Donald GWilliams, Nigel MPittman, AlanGan-Or, ZivFernandez-Santiago, RubenBrice, AlexisLesage, SuzanneFarrer, MatthewWood, NicholasMorris, Huw R2023-02-092023-02-092020-07-03Brown 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.http://hdl.handle.net/10668/16190The 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 Our analysis of DNM3 in previously unpublished data does not show an effect on age at onset in LRRK2 p.G2019S carriers; however, the inter-study heterogeneity may indicate ethnic or population-specific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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Genetic modifiersLeucine-rich repeat kinase 2ParkinsonismParkinson’s diseaseAge of OnsetAgedCohort StudiesDynamin IIIEpistasis, GeneticFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGenetic VariationHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Linkage DisequilibriumMaleMiddle AgedParkinson DiseaseR-SNARE ProteinsRiskresearch article32873436open accessAncianoDesequilibrio de ligamientoDinamina IIIEdad de inicioEnfermedad de ParkinsonEpistasis genéticaEstudios de asociación genéticaEstudios de cohortesPredisposición genética a la enfermedadProteína 2 quinasa serina-treonina rica en repeticiones de leucinaProteínas R-SNARERiesgoVariación genética10.1016/j.neurobiolaging.2020.07.0021558-1497PMC7762821https://doi.org/10.1016/j.neurobiolaging.2020.07.002