TY  - JOUR
AU  - Brown, Emmeline E
AU  - Blauwendraat, Cornelis
AU  - Trinh, Joanne
AU  - Rizig, Mie
AU  - Nalls, Mike A
AU  - Leveille, Etienne
AU  - Ruskey, Jennifer A
AU  - Jonvik, Hallgeir
AU  - Tan, Manuela M X
AU  - Bandres-Ciga, Sara
AU  - Hassin-Baer, Sharon
AU  - Brockmann, Kathrin
AU  - Infante, Jon
AU  - Tolosa, Eduardo
AU  - Ezquerra, Mario
AU  - Ben Romdhan, Sawssan
AU  - Benmahdjoub, Mustapha
AU  - Arezki, Mohamed
AU  - Mhiri, Chokri
AU  - Hardy, John
AU  - Singleton, Andrew B
AU  - Alcalay, Roy N
AU  - Gasser, Thomas
AU  - Grosset, Donald G
AU  - Williams, Nigel M
AU  - Pittman, Alan
AU  - Gan-Or, Ziv
AU  - Fernández-Santiago, Rubén
AU  - Brice, Alexis
AU  - Lesage, Suzanne
AU  - Farrer, Matthew
AU  - Wood, Nicholas
AU  - Morris, Huw R
TI  - Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson's disease.
JO  - Neurobiology of aging
VL  - 97
SN  - 0197-4580
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DZNE-2021-00876
SP  - 148.e17 - 148.e24
PY  - 2021
AB  - 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 Our analysis of DNM3 in previously unpublished data does not show an effect on age at onset in LRRK2 p.G2019S carriers; however, the inter-study heterogeneity may indicate ethnic or population-specific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.
KW  - Age of Onset
KW  - Aged
KW  - Cohort Studies
KW  - Dynamin III: genetics
KW  - Epistasis, Genetic: genetics
KW  - Female
KW  - Genetic Association Studies
KW  - Genetic Predisposition to Disease: genetics
KW  - Genetic Variation: genetics
KW  - Humans
KW  - Leucine-Rich Repeat Serine-Threonine Protein Kinase-2: genetics
KW  - Linkage Disequilibrium: genetics
KW  - Male
KW  - Middle Aged
KW  - Parkinson Disease: epidemiology
KW  - Parkinson Disease: ethnology
KW  - Parkinson Disease: genetics
KW  - R-SNARE Proteins: genetics
KW  - Risk
KW  - Genetic modifiers (Other)
KW  - Leucine-rich repeat kinase 2 (Other)
KW  - Parkinsonism (Other)
KW  - Parkinson’s disease (Other)
KW  - R-SNARE Proteins (NLM Chemicals)
KW  - VAMP4 protein, human (NLM Chemicals)
KW  - LRRK2 protein, human (NLM Chemicals)
KW  - Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (NLM Chemicals)
KW  - Dynamin III (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:32873436
C2  - pmc:PMC7762821
DO  - DOI:10.1016/j.neurobiolaging.2020.07.002
UR  - https://pub.dzne.de/record/155708
ER  -