Abstract
A recent study MacLeod et al. has shown that an interaction between variants at the LRRK2 and PARK16 loci influences risk of development of Parkinson's disease (PD). Our study examines the proposed interaction between LRRK2 and PARK16 variants in modifying PD risk using a large multicenter series of PD patients (7715) and controls (8261) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Our data does not support a strong direct interaction between LRRK2 and PARK16 variants; however, given the role of retromer and lysosomal pathways in PD, further studies are warranted.
Original language | English |
---|---|
Pages (from-to) | 217.e1-217.e4 |
Journal | Neurobiology of Aging |
Volume | 49 |
DOIs | |
Publication status | Published - 1 Jan 2017 |
Externally published | Yes |
Keywords
- Genetic epidemiology
- LRRK2
- PARK16
- Parkinson's disease
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In: Neurobiology of Aging, Vol. 49, 01.01.2017, p. 217.e1-217.e4.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Evaluation of the interaction between LRRK2 and PARK16 loci in determining risk of Parkinson's disease
T2 - analysis of a large multicenter study
AU - Wang, Lisa
AU - Heckman, Michael G.
AU - Aasly, Jan O.
AU - Annesi, Grazia
AU - Bozi, Maria
AU - Chung, Sun Ju
AU - Clarke, Carl
AU - Crosiers, David
AU - Eckstein, Gertrud
AU - Garraux, Gaetan
AU - Hadjigeorgiou, Georgios M.
AU - Hattori, Nobu
AU - Jeon, Beom
AU - Kim, Yun J.
AU - Kubo, Masato
AU - Lesage, Suzanne
AU - Lin, Juei Jueng
AU - Lynch, Timothy
AU - Lichtner, Peter
AU - Mellick, George D.
AU - Mok, Vincent
AU - Morrison, Karin E.
AU - Quattrone, Aldo
AU - Satake, Wataru
AU - Silburn, Peter A.
AU - Stefanis, Leonidas
AU - Stockton, Joanne D.
AU - Tan, Eng King
AU - Toda, Tatsushi
AU - Brice, Alexis
AU - Van Broeckhoven, Christine
AU - Uitti, Ryan J.
AU - Wirdefeldt, Karin
AU - Wszolek, Zbigniew
AU - Xiromerisiou, Georgia
AU - Maraganore, Demetrius M.
AU - Gasser, Thomas
AU - Krüger, Rejko
AU - Farrer, Matthew J.
AU - Ross, Owen A.
AU - Sharma, Manu
N1 - Funding Information: The Mayo Clinic Jacksonville is a Morris K. Udall Center of Excellence in Parkinson's Disease Research (grant number P50 NS072187) and was supported by the gift from the family of Carl Edward Bolch, Jr., and Susan Bass Bolch (RJU, ZKW, OAR). Owen A. Ross, PhD, acknowledges funding support from the National Institutes of Health (grant number R01 NS78086 ). M. J. Farrer reports grants from the Canadian Federal Government , Cunhill Foundation , BC Leading Edge Endowment , during the conduct of the study; also personal fees from Gentech, personal fees from Teva, outside the submitted work. B. Jeon has received funding for travel from GlaxoSmithKline Korea and Novartis Korea; and has received research support as PI from Norvartis, Boehringer Ingelheim, Ipsen Korea, the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (#A030001), ABRC (Advanced Biometric Research Center), KOSEF (Korea Science and Engineering Foundation), Seoul National University Hospital, the Mr Chung Suk-Gyoo and Sinyang Cultural Foundation, and the Song Foundation. Dr Lynch has served on an advisory board for Biogen and Novartis and has received honoraria from Lundbeck, Biogen, and Boerhinger-Ingelheim, and received funding from the NIH (Grant number: 1(GG010270)). Demetrius M. Maraganore, MD acknowledges the National Institutes of Health for funding support (grant number R01ES10751 ). E. K. Tan is funded by National Medical Research Council (RIE 2015 PD TCR and STaR), Duke-NUS Graduate Medical School (non grant support) and has received honoraria from Novartis, Boehringer Ingelheim and GSK. R. J. Uitti has received research funding from the NIH , PARRF , PSG , Noscira, Inc , and Advanced Neuromodulation Systems, Inc . Dr. Wszolek and Dr. Uitti are partially supported by the NIH/NINDS P50 NS072187, NIH/NIA (primary) and NIH/NINDS (secondary) 1U01AG045390-01A1, Mayo Clinic Center for Regenerative Medicine, Mayo Clinic Center for Individualized Medicine, Mayo Clinic Neuroscience Focused Research Team (Cecilia and Dan Carmichael Family Foundation, and the James C. and Sarah K. Kennedy Fund for Neurodegenerative Disease Research at Mayo Clinic in Florida), the gift from Carl Edward Bolch, Jr., and Susan Bass Bolch, The Sol Goldman Charitable Trust, and Donald G. and Jodi P. Heeringa. Funding for Prof. Gasser was provided by the German Center for Neurodegenerative Diseases (DZNE) through the CoEN initiative (www.coen.org), German Research Foundation (GA 402/18-1), Federal Ministry of Education and Research (031A430A and 01ED1406) and Michael J. Fox Foundation (PPMI project). He received speakers' honoraria from Novartis, Merck-Serono, Schwarz Pharma, Boehringer Ingelheim, and Valeant Pharma and royalties for his consulting activities from Cefalon Pharma and Merck-Serono. R. Krüger has received research grants of the German Research Council (DFG; KR2119/8-1), the Fritz Thyssen Foundation ((10.11.2.153, Germany) and the Fond National de Recherche (PEARL [FNR/P13/6682797/Krüger]; NCER-PD, Luxembourg), as well as speakers' honoraria and/or travel grants from Abbvie, St. Jude and Medtronic. Studies at individual sites were supported by a number of different funding agencies world-wide including; Italian Ministry of Health (Ricerca Corrente, Ricerca Finalizzata); the Swedish Parkinson Foundation (697/14); the Federal Ministry of Education and Research (BMBF, NGFNplus; 01GS08134] (RK); the NGFNplus (Neuron-Parkinson-subproject 7) (SG); CHRU de Lille, UnivLille 2, Inserm; French Ministry PHRCs (1994/, 2002/1918, 2005/1914); Association France Parkinson (2005); Fondation de France 2004-013306; Fondation de la Recherche Médicale (2006); PPF (synucléothèque 2005-2009); the 2 Centres de Ressources Biologiques (IPL-Lille, CHRU-Lille) and its scientific committee (AD, MCCH, Philippe Amouyel, Florence Pasquier, Régis Bordet); funding from France-Parkinson Association (R16058DD) and the program “Investissement d'avenir” ANR-10-IAIHU-06; the Swedish Research Council; the Swedish Society for Medical Research; the Swedish Society of Medicine; funds from the Karolinska Institutet , the National Institutes of Health and National Institute of Neurological Disorders and Stroke [grant numbers 1RC2NS070276 , NS057567 , and P50NS072187 ]; Mayo Clinic Florida Research Committee CR programs (MJF) (ZKW); the Geriatric Medical Foundation of Queensland (GDM); a career development award from the Volkswagen Foundation and from the Hermann and Lilly Schilling Foundation (CK); the Research Committee of University of Thessaly (Code: 2845); the Queensland Parkinson's Project: R.S Boyle and A Sellbach (Proncess Alexandra Hospital, Brisbane), J.D. O'Sullivan (Royal Brisbane and Women's Hospital Brisbane), G.T. Sutherland, G.A Siebert and N.N.W Dissanayaka (Eskitis Institute for Cell and Molecular Therapies, Griffith University, Nathan, QLD), Belgian Science Policy Office Interuniversity Attraction Poles program, Belgium; the Alzheimer Research Foundation (SAO-FRA), Belgium; the Flemish Government initiated Methusalem Excellence program, Belgium; the Research Foundation Flanders (FWO), Belgium; the Agency for Innovation by Science and Technology Flanders (IWT), Belgium and the University of Antwerp Research Fund, Belgium; The Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and development, AMED and Grant-in-Aid for Young Scientists A (25713015) from the Japan Society for the Promotion of Science, JSPS; and the Laboratory of Neurogenetics, Biomedicine Department, CERETETH, Larissa, Greece (Code: 01-04-207) (GH, ED). Funding Information: The institution of L. Wang and M. Sharma is financially supported by the Courage-PD, an EU Joint Programme-Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organizations under the aegis of JPND- www.jpnd.eu : the Medical Research Council, United Kingdom, the French National Research Agency, the German Bundesministerium für Bildung und Forschung, the Italian Ministry of Health/Ministry of Education, the Israeli Ministry of Health, the Luxembourgian National Research Fund, the Netherlands Organisation for Health Research and Development, the Research Council of Norway, the Portuguese Foundation for Science and Technology, the Spanish National Institute of Health Carlos III and Michael J. Fox Foundation. M. J. Farrer has a patent on genetic variability in LRRK2 and Parkinson's disease (US8409809, US8455243B2) and on LRRK2 mouse models subsequently developed with royalities paid. Nobutaka Hattori has been serving as an advisory board member for Boehringer Ingelheim, as a result of attending advisory board meetings he received personal compensation; he also has been serving as an advisory board member for FP Pharmaceutical Company, by attending these advisory meetings he received personal compensation and has been consulting with Ohtsuska Pharmaceutical Company, Kyowa Hakko Kirin Pharmaceutical Company, GlaxoSmithKline, Novartis, and Schering-Plough, and when he attended these advisory board meetings where he received personal compensation. Dr Gasser holds a patent concerning the LRRK2 gene and neurodegenerative disorders. Publisher Copyright: © 2016 Elsevier Inc.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - A recent study MacLeod et al. has shown that an interaction between variants at the LRRK2 and PARK16 loci influences risk of development of Parkinson's disease (PD). Our study examines the proposed interaction between LRRK2 and PARK16 variants in modifying PD risk using a large multicenter series of PD patients (7715) and controls (8261) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Our data does not support a strong direct interaction between LRRK2 and PARK16 variants; however, given the role of retromer and lysosomal pathways in PD, further studies are warranted.
AB - A recent study MacLeod et al. has shown that an interaction between variants at the LRRK2 and PARK16 loci influences risk of development of Parkinson's disease (PD). Our study examines the proposed interaction between LRRK2 and PARK16 variants in modifying PD risk using a large multicenter series of PD patients (7715) and controls (8261) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Our data does not support a strong direct interaction between LRRK2 and PARK16 variants; however, given the role of retromer and lysosomal pathways in PD, further studies are warranted.
KW - Genetic epidemiology
KW - LRRK2
KW - PARK16
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=85002145842&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2016.09.022
DO - 10.1016/j.neurobiolaging.2016.09.022
M3 - Article
C2 - 27814993
AN - SCOPUS:85002145842
SN - 0197-4580
VL - 49
SP - 217.e1-217.e4
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -