Journal Article

DZNE-2021-00876

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson's disease.

Brown, E. E. ; Blauwendraat, C.Extern* ; Trinh, J. ; Rizig, M. ; Nalls, M. A. ; Leveille, E. ; Ruskey, J. A. ; Jonvik, H. ; Tan, M. M. X. ; Bandres-Ciga, S. ; Hassin-Baer, S. ; Brockmann, K.Extern* ; Infante, J. ; Tolosa, E. ; Ezquerra, M. ; Ben Romdhan, S. ; Benmahdjoub, M. ; Arezki, M. ; Mhiri, C. ; Hardy, J. ; Singleton, A. B. ; Alcalay, R. N. ; Gasser, T.DZNE* ; Grosset, D. G. ; Williams, N. M. ; Pittman, A. ; Gan-Or, Z. ; Fernández-Santiago, R.Extern* ; Brice, A. ; Lesage, S. ; Farrer, M. ; Wood, N. ; Morris, H. R. ; Consortium, I. P. D. G. (Collaboration Author)

2021
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.neurobiolaging.2020.07.002

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 Our analysis of DNM3 in previously unpublished data does not show an effect on age at onset in LRRK2 p.G2019S carriers; however, the inter-study heterogeneity may indicate ethnic or population-specific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.

Keyword(s): Age of Onset (MeSH) ; Aged (MeSH) ; Cohort Studies (MeSH) ; Dynamin III: genetics (MeSH) ; Epistasis, Genetic: genetics (MeSH) ; Female (MeSH) ; Genetic Association Studies (MeSH) ; Genetic Predisposition to Disease: genetics (MeSH) ; Genetic Variation: genetics (MeSH) ; Humans (MeSH) ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2: genetics (MeSH) ; Linkage Disequilibrium: genetics (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Parkinson Disease: epidemiology (MeSH) ; Parkinson Disease: ethnology (MeSH) ; Parkinson Disease: genetics (MeSH) ; R-SNARE Proteins: genetics (MeSH) ; Risk (MeSH) ; Genetic modifiers ; Leucine-rich repeat kinase 2 ; Parkinsonism ; Parkinson’s disease ; R-SNARE Proteins ; VAMP4 protein, human ; LRRK2 protein, human ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ; Dynamin III

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Contributing Institute(s):

1. Parkinson Genetics (AG Gasser)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2021

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