Evaluation of the interaction between LRRK2 and PARK16 loci in determining risk of Parkinson's disease: analysis of a large multicenter study.
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.
Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tuebingen, Tuebingen, Germany.
Lisa
L
Wang
Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL, USA.
Michael G
MG
Heckman
Department of Neurology, St Olavs Hospital and NTNU, Trondheim, Norway.
Jan O
JO
Aasly
Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, Italy.
Grazia
G
Annesi
Neurology Department, Psychiatry Athens Hospital, Athens, Greece; 2nd Neurology Clinic, University of Athens, Attikon Hospital, Athens, Greece.
Maria
M
Bozi
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Sun Ju
SJ
Chung
School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK; Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Carl
C
Clarke
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Department of Neurology, University Hospital Antwerp, Antwerp, Belgium.
David
D
Crosiers
Helmholtz Zentrum München, German Research Centre for Environmental Health (Gmbh), Neuherberg, Germany.
Gertrud
G
Eckstein
Department of Neurology, Cyclotron Research Centre, University of Liège, Liège, Belgium.
Gaetan
G
Garraux
Department of Neurology, Faculty of Medicine, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece.
Georgios M
GM
Hadjigeorgiou
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Nobu
N
Hattori
Institute Department of Neurology, Seoul National University Hospital, Seoul, Korea.
Beom
B
Jeon
ILSONG Institute of Life Science, Hallym University, Hallym Institute of Translational Genomics and Bioinformatics, Department of Neurology, Hallym University Sacred Heart Hospital, Gangwon, Korea.
Yun J
YJ
Kim
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Masato
M
Kubo
INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
Suzanne
S
Lesage
Department of Neurology, Chushang Show-Chwan Hospital, Nantou, Taiwan; Department of Neurology, Chung-Shan Medical University Hospital, Taichung, Taiwan.
Juei Jueng
JJ
Lin
The Dublin Neurological Institute at the Mater Misericordiae University Hospital, and Conway Institute, University College Dublin, Dublin, Ireland.
Timothy
T
Lynch
Helmholtz Zentrum München, German Research Centre for Environmental Health (Gmbh), Neuherberg, Germany.
Peter
P
Lichtner
Eskitis Institute for Cell and Molecular Therapies, Griffith University, Queensland, Australia.
George D
GD
Mellick
Therese Pei Fong Chow Research Center for Prevention of Dementia, Faculty of Medicine, The Chinese University of Hong Kong, Department of Medicine & Therapeutics, Clinical Neurology Research Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, New Territories, Hong Kong.
Vincent
V
Mok
Faculty of Medicine, University of Southampton, Southampton, UK.
Karin E
KE
Morrison
Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, Italy; Department of Medical Sciences, Institute of Neurology, University Magna Graecia, Catanzaro, Italy.
Aldo
A
Quattrone
Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan.
Wataru
W
Satake
University of Queensland Centre for Clinical Research, Herston, Australia.
Peter A
PA
Silburn
2nd Neurology Clinic, University of Athens, Attikon Hospital, Athens, Greece; Divisions of Basic Neurosciences and Cell Biology, Biomedical Research Foundation of Academy of Athens, Athens, Greece.
Leonidas
L
Stefanis
Neurosciences Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Joanne D
JD
Stockton
Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore; Programme in Neuroscience and Behavior Disorders, Duke-NUS Graduate Medical School, Durham, NC, USA.
Eng King
EK
Tan
Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan.
Tatsushi
T
Toda
INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
Alexis
A
Brice
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
Christine
C
Van Broeckhoven
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Ryan J
RJ
Uitti
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
Karin
K
Wirdefeldt
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Zbigniew
Z
Wszolek
Department of Neurology, Faculty of Medicine, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece.
Georgia
G
Xiromerisiou
Department of Neurology, NorthShore University HealthSystem, Evanston, IL, USA.
Demetrius M
DM
Maraganore
Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Science Research, University of Tuebingen, Tuebingen, Germany.
Thomas
T
Gasser
Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Science Research, University of Tuebingen, Tuebingen, Germany; Clinical and Experimental Neuroscience, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Luxembourg City, Luxembourg; Centre Hospitalier de Luxembourg (CHL), Luxembourg City, Luxembourg.
Rejko
R
Krüger
Djavad Mowafhagian Centre for Brain, University of British Columbia, Vancouver, British Columbia, Canada.
Matthew J
MJ
Farrer
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
Owen A
OA
Ross
Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tuebingen, Tuebingen, Germany; Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Science Research, University of Tuebingen, Tuebingen, Germany. Electronic address: manu.sharma@uni-tuebingen.de.
Manu
M
Sharma
D004843:Epistasis, Genetic / Q000235:genetics*; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D015337:Multicenter Studies as Topic; D010300:Parkinson Disease / Q000235:genetics*; D012306:Risk
C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
Genetic epidemiology; LRRK2; PARK16; Parkinson's disease