TY - JOUR
T1 - Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson's disease
AU - International Parkinson Disease Genomics Consortium (IPDGC)
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 - Fernandez-Santiago, Ruben
AU - Brice, Alexis
AU - Lesage, Suzanne
AU - Farrer, Matthew
AU - Wood, Nicholas
AU - Morris, Huw R.
N1 - Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2020/7/13
Y1 - 2020/7/13
N2 - 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 Our analysis of DNM3 in previously unpublished data does not show an effect on age at onset in LRRK2 p.G2019S carriers; however, the inter-study heterogeneity may indicate ethnic or population-specific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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85090061408&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/0dc36c94-0ecb-38b9-aba0-8a2d7a8f6d6c/
U2 - 10.1016/j.neurobiolaging.2020.07.002
DO - 10.1016/j.neurobiolaging.2020.07.002
M3 - Journal articles
C2 - 32873436
AN - SCOPUS:85090061408
SN - 0197-4580
VL - 97
SP - 148.e17-148.e24
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -