RT Journal Article
T1 Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson's disease.
A1 Brown, Emmeline E
A1 Blauwendraat, Cornelis
A1 Trinh, Joanne
A1 Rizig, Mie
A1 Nalls, Mike A
A1 Leveille, Etienne
A1 Ruskey, Jennifer A
A1 Jonvik, Hallgeir
A1 Tan, Manuela M X
A1 Bandres-Ciga, Sara
A1 Hassin-Baer, Sharon
A1 Brockmann, Kathrin
A1 Infante, Jon
A1 Tolosa, Eduardo
A1 Ezquerra, Mario
A1 Ben Romdhan, Sawssan
A1 Benmahdjoub, Mustapha
A1 Arezki, Mohamed
A1 Mhiri, Chokri
A1 Hardy, John
A1 Singleton, Andrew B
A1 Alcalay, Roy N
A1 Gasser, Thomas
A1 Grosset, Donald G
A1 Williams, Nigel M
A1 Pittman, Alan
A1 Gan-Or, Ziv
A1 Fernandez-Santiago, Ruben
A1 Brice, Alexis
A1 Lesage, Suzanne
A1 Farrer, Matthew
A1 Wood, Nicholas
A1 Morris, Huw R
K1 Genetic modifiers
K1 Leucine-rich repeat kinase 2
K1 Parkinsonism
K1 Parkinson’s disease
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 Our analysis of DNM3 in previously unpublished data does not show an effect on age at onset in LRRK2 p.G2019S carriers; however, the inter-study heterogeneity may indicate ethnic or population-specific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.
PB Elsevier Inc.
YR 2020
FD 2020-07-03
LK http://hdl.handle.net/10668/16190
UL http://hdl.handle.net/10668/16190
LA en
NO 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.
NO The authors would like to thank all of the Parkinson’s disease patients and unaffected relatives who donated their time and biological samples to be part of this study. The authors would also like to thank all members of the International Parkinson Disease Genomics Consortium (IPDGC). For a complete overview of IPDGC members, acknowledgments, and funding, please see http://pdgenetics.org/partners . This work was supported by Parkinson's UK (grant numbers: J-1101, H-1703), University College London (UCL), the NIHR Rare Diseases Translational Research Consortium, the Medical Research Council (MRC) (award number MR/N026004/1), the Intramural Research Programs of the National Institute of Neurological Disorders, and Stroke (NINDS) and the National Institute on Aging (NIA), UK Dementia Research Institute which receives its funding from DRI Ltd (funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK), Alzheimer's Society and Alzheimer’s Research UK, Wellcome Trust Hardy (award number 202903/Z/16/Z), Dolby Family Fund, National Institute for Health Research University College London Hospitals Biomedical Research Centre, BRCNIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London. Funding sources had no involvement in study design, collection, analysis and interpretation of data.
DS RISalud
RD Apr 6, 2025