| Literature DB >> 32873436 |
Emmeline E Brown1, Cornelis Blauwendraat2, Joanne Trinh3, Mie Rizig1, Mike A Nalls4, Etienne Leveille5, Jennifer A Ruskey5, Hallgeir Jonvik1, Manuela M X Tan1, Sara Bandres-Ciga6, Sharon Hassin-Baer7, Kathrin Brockmann8, Jon Infante9, Eduardo Tolosa10, Mario Ezquerra10, Sawssan Ben Romdhan11, Mustapha Benmahdjoub12, Mohamed Arezki12, Chokri Mhiri12, John Hardy13, Andrew B Singleton2, Roy N Alcalay14, Thomas Gasser15, Donald G Grosset16, Nigel M Williams17, Alan Pittman18, Ziv Gan-Or19, Ruben Fernandez-Santiago10, Alexis Brice20, Suzanne Lesage20, Matthew Farrer21, Nicholas Wood1, Huw R Morris22.
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 Our analysis of DNM3 in previously unpublished data does not show an effect on age at onset in LRRK2 p.G2019S carriers; however, the inter-study heterogeneity may indicate ethnic or population-specific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.Entities:
Keywords: Genetic modifiers; Leucine-rich repeat kinase 2; Parkinsonism; Parkinson’s disease
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Year: 2020 PMID： 32873436 PMCID： PMC7762821 DOI： 10.1016/j.neurobiolaging.2020.07.002
Source DB: PubMed Journal: Neurobiol Aging ISSN： 0197-4580 Impact factor: 4.673