Evaluation of the interaction between LRRK2 and PARK16 loci in determining risk of Parkinson's disease: analysis of a large multicenter study

Lisa Wang; Michael G Heckman; Jan O Aasly; Grazia Annesi; Maria Bozi; Sun Ju Chung; Carl Clarke; David Crosiers; Gertrud Eckstein; Gaetan Garraux; Georgios M Hadjigeorgiou; Nobu Hattori; Beom Jeon; Yun J Kim; Masato Kubo; Suzanne Lesage; Juei Jueng Lin; Timothy Lynch; Peter Lichtner; George D Mellick; Vincent Mok; Karin E Morrison; Aldo Quattrone; Wataru Satake; Peter A Silburn; Leonidas Stefanis; Joanne D Stockton; Eng King Tan; Tatsushi Toda; Alexis Brice; Christine Van Broeckhoven; Ryan J Uitti; Karin Wirdefeldt; Zbigniew Wszolek; Georgia Xiromerisiou; Demetrius M Maraganore; Thomas Gasser; Rejko Krüger; Matthew J Farrer; Owen A Ross; Manu Sharma; GEOPD Consortium

doi:10.1016/j.neurobiolaging.2016.09.022

Evaluation of the interaction between LRRK2 and PARK16 loci in determining risk of Parkinson's disease: analysis of a large multicenter study

Neurobiol Aging. 2017 Jan:49:217.e1-217.e4. doi: 10.1016/j.neurobiolaging.2016.09.022. Epub 2016 Oct 6.

Authors

Lisa Wang¹, Michael G Heckman², Jan O Aasly³, Grazia Annesi⁴, Maria Bozi⁵, Sun Ju Chung⁶, Carl Clarke⁷, David Crosiers⁸, Gertrud Eckstein⁹, Gaetan Garraux¹⁰, Georgios M Hadjigeorgiou¹¹, Nobu Hattori¹², Beom Jeon¹³, Yun J Kim¹⁴, Masato Kubo¹⁵, Suzanne Lesage¹⁶, Juei Jueng Lin¹⁷, Timothy Lynch¹⁸, Peter Lichtner⁹, George D Mellick¹⁹, Vincent Mok²⁰, Karin E Morrison²¹, Aldo Quattrone²², Wataru Satake²³, Peter A Silburn²⁴, Leonidas Stefanis²⁵, Joanne D Stockton²⁶, Eng King Tan²⁷, Tatsushi Toda²³, Alexis Brice¹⁶, Christine Van Broeckhoven²⁸, Ryan J Uitti²⁹, Karin Wirdefeldt³⁰, Zbigniew Wszolek²⁹, Georgia Xiromerisiou¹¹, Demetrius M Maraganore³¹, Thomas Gasser³², Rejko Krüger³³, Matthew J Farrer³⁴, Owen A Ross³⁵, Manu Sharma³⁶; GEOPD Consortium

Affiliations

¹ Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tuebingen, Tuebingen, Germany.
² Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, FL, USA.
³ Department of Neurology, St Olavs Hospital and NTNU, Trondheim, Norway.
⁴ Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, Italy.
⁵ Neurology Department, Psychiatry Athens Hospital, Athens, Greece; 2nd Neurology Clinic, University of Athens, Attikon Hospital, Athens, Greece.
⁶ Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁷ 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.
⁸ Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium; Department of Neurology, University Hospital Antwerp, Antwerp, Belgium.
⁹ Helmholtz Zentrum München, German Research Centre for Environmental Health (Gmbh), Neuherberg, Germany.
¹⁰ Department of Neurology, Cyclotron Research Centre, University of Liège, Liège, Belgium.
¹¹ Department of Neurology, Faculty of Medicine, University of Thessaly and Institute of Biomedical Research and Technology, CERETETH, Larissa, Greece.
¹² Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
¹³ Institute Department of Neurology, Seoul National University Hospital, Seoul, Korea.
¹⁴ ILSONG Institute of Life Science, Hallym University, Hallym Institute of Translational Genomics and Bioinformatics, Department of Neurology, Hallym University Sacred Heart Hospital, Gangwon, Korea.
¹⁵ Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
¹⁶ 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.
¹⁷ Department of Neurology, Chushang Show-Chwan Hospital, Nantou, Taiwan; Department of Neurology, Chung-Shan Medical University Hospital, Taichung, Taiwan.
¹⁸ The Dublin Neurological Institute at the Mater Misericordiae University Hospital, and Conway Institute, University College Dublin, Dublin, Ireland.
¹⁹ Eskitis Institute for Cell and Molecular Therapies, Griffith University, Queensland, Australia.
²⁰ 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.
²¹ Faculty of Medicine, University of Southampton, Southampton, UK.
²² Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, Italy; Department of Medical Sciences, Institute of Neurology, University Magna Graecia, Catanzaro, Italy.
²³ Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan.
²⁴ University of Queensland Centre for Clinical Research, Herston, Australia.
²⁵ 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.
²⁶ Neurosciences Department, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
²⁷ Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore; Programme in Neuroscience and Behavior Disorders, Duke-NUS Graduate Medical School, Durham, NC, USA.
²⁸ Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
²⁹ Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
³⁰ Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
³¹ Department of Neurology, NorthShore University HealthSystem, Evanston, IL, USA.
³² Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Science Research, University of Tuebingen, Tuebingen, Germany.
³³ 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.
³⁴ Djavad Mowafhagian Centre for Brain, University of British Columbia, Vancouver, British Columbia, Canada.
³⁵ Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
³⁶ 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.

PMID: 27814993
PMCID: PMC5154911
DOI: 10.1016/j.neurobiolaging.2016.09.022

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.

Keywords: Genetic epidemiology; LRRK2; PARK16; Parkinson's disease.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Epistasis, Genetic / genetics*
Genetic Association Studies*
Genetic Loci / genetics*
Genetic Predisposition to Disease / genetics*
Genetic Variation / genetics*
Humans
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics*
Multicenter Studies as Topic*
Parkinson Disease / genetics*
Risk

Evaluation of the interaction between LRRK2 and PARK16 loci in determining risk of Parkinson's disease: analysis of a large multicenter study

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

Supplementary concepts

Grants and funding