Publication: Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson's disease.
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Identifiers
Date
2020-07-03
Authors
Brown, Emmeline E
Blauwendraat, Cornelis
Trinh, Joanne
Rizig, Mie
Nalls, Mike A
Leveille, Etienne
Ruskey, Jennifer A
Jonvik, Hallgeir
Tan, Manuela M X
Bandres-Ciga, Sara
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier Inc.
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 Our analysis of DNM3 in previously unpublished data does not show an effect on age at onset in LRRK2 p.G2019S carriers; however, the inter-study heterogeneity may indicate ethnic or population-specific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.
Description
MeSH Terms
Age of Onset
Aged
Cohort Studies
Dynamin III
Epistasis, Genetic
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Variation
Humans
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
Linkage Disequilibrium
Male
Middle Aged
Parkinson Disease
R-SNARE Proteins
Risk
Aged
Cohort Studies
Dynamin III
Epistasis, Genetic
Female
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Variation
Humans
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
Linkage Disequilibrium
Male
Middle Aged
Parkinson Disease
R-SNARE Proteins
Risk
DeCS Terms
Anciano
Desequilibrio de ligamiento
Dinamina III
Edad de inicio
Enfermedad de Parkinson
Epistasis genética
Estudios de asociación genética
Estudios de cohortes
Predisposición genética a la enfermedad
Proteína 2 quinasa serina-treonina rica en repeticiones de leucina
Proteínas R-SNARE
Riesgo
Variación genética
Desequilibrio de ligamiento
Dinamina III
Edad de inicio
Enfermedad de Parkinson
Epistasis genética
Estudios de asociación genética
Estudios de cohortes
Predisposición genética a la enfermedad
Proteína 2 quinasa serina-treonina rica en repeticiones de leucina
Proteínas R-SNARE
Riesgo
Variación genética
CIE Terms
Keywords
Genetic modifiers, Leucine-rich repeat kinase 2, Parkinsonism, Parkinson’s disease
Citation
Brown 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.