Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers.
Journal: Movement disorders : official journal of the Movement Disorder Society
Volume: 38
Issue: 4
Year of Publication: 2023
Affiliated Institutions:
Université Paris-Saclay, UVSQ, Inserm, Gustave Roussy, Team "Exposome, Heredity, Cancer and Health", CESP, Villejuif, France.
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Institute for Clinical and Translational Research, Baylor Medical College of Medecine, Houston, Texas, USA.
International Agency for Research on Cancer, Lyon, France.
Lunenfeld-Tanenbuaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, Institut de Biologie François Jacob, Evry, France.
Inserm, U, Institut Curie, PSL University, Mines ParisTech, Paris, France.
Université Paris-Saclay, UVSQ, Gustave Roussy, Inserm, Team "Epidemiology of radiations," CESP, Villejuif, France.
Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Tübingen, Germany.
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tubingen, Tübingen, Germany.
Translational Neuroscience, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-Belval, Luxembourg.
Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Griffith Institute for Drug Discovery, Griffith University, Nathan, Australia.
Department of Neurology, Medical University of Vienna, Vienna, Austria.
Department of Neurology, Klinik Ottakring, Vienna, Austria.
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada.
Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, Australia.
Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
Department of Neurology, Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, INSERM, CNRS, Assistance Publique Hôpitaux de Paris, Paris, France.
Université de Lille, Inserm, CHU Lille, UMR-S , LilNCog, Centre de Recherche Lille Neurosciences & Cognition, Lille, France.
Department of Neurology, Ludwig Maximilians University of Munich, Munich, Germany.
Department of Neurology and Department of Clinical Genomics, Mayo Clinic Florida, Jacksonville, Florida, USA.
Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Department of Molecular Medicine, University of Pavia, Pavia, Italy.
UOC Medical Genetics and Advanced Cell Diagnostics, S. Andrea University Hospital, Rome, Italy.
Department of Biomedical Sciences, Humanitas University, Milan, Italy.
Parkinson Institute, Azienda Socio Sanitaria Territoriale (ASST) Gaetano Pini/CTO, Milan, Italy.
Parkinson Institute, Fontazione Grigioni-Via Zuretti, Milan, Italy.
Department of Neurology, San Gerardo Hospital, Monza, Italy.
Institute for Biomedical Research and Innovation, National Research Council, Cosenza, Italy.
Institute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy.
Department of Medical and Surgical Sciences, Neuroscience Research Center, Magna Graecia University, Catanzaro, Italy.
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama, Japan.
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.
Neurology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
Department of Neurology, Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands.
Department of Neurology, St. Olav's Hospital and Norwegian University of Science and Technology, Trondheim, Norway.
Department of Neurology, Oslo University Hospital, Oslo, Norway.
Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
Parkinson's Disease & Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Lab of Parkinson's disease and Other Neurodegenerative Movement Disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
Unit of Neurodegenerative Diseases, Department of Neurology, University Hospital Germans Trias i Pujol, Barcelona, Spain.
Fundació per la Recerca Biomèdica i Social Mútua Terrassa, Barcelona, Spain.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Neurology, Lund, Sweden.
University of Birmingham and Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom.
Faculty of Medicine, Health and Life Sciences, Queens University, Belfast, United Kingdom.
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
German Center for Neurodegenerative Diseases, Tübingen, Germany.
Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA.
Abstract summary
Epidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties.We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors.We used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses.We confirmed a previously reported positive genetic correlation of PD with melanoma (G = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (G = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31).We show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Authors & Co-authors:
Sugier Pierre-Emmanuel PE
Lucotte Elise A EA
Domenighetti Cloé C
Law Matthew H MH
Iles Mark M MM
Brown Kevin K
Amos Christopher C
McKay James D JD
Hung Rayjean J RJ
Karimi Mojgan M
Bacq-Daian Delphine D
Boland-Augé Anne A
Olaso Robert R
Deleuze Jean-François JF
Lesueur Fabienne F
Ostroumova Evgenia E
Kesminiene Ausrele A
de Vathaire Florent F
Guénel Pascal P
Sreelatha Ashwin Ashok Kumar AAK
Schulte Claudia C
Grover Sandeep S
May Patrick P
Bobbili Dheeraj R DR
Radivojkov-Blagojevic Milena M
Lichtner Peter P
Singleton Andrew B AB
Hernandez Dena G DG
Edsall Connor C
Mellick George D GD
Zimprich Alexander A
Pirker Walter W
Rogaeva Ekaterina E
Lang Anthony E AE
Koks Sulev S
Taba Pille P
Lesage Suzanne S
Brice Alexis A
Corvol Jean-Christophe JC
Chartier-Harlin Marie-Christine MC
Mutez Eugénie E
Brockmann Kathrin K
Deutschländer Angela B AB
Hadjigeorgiou Georges M GM
Dardiotis Efthimios E
Stefanis Leonidas L
Simitsi Athina Maria AM
Valente Enza Maria EM
Petrucci Simona S
Straniero Letizia L
Zecchinelli Anna A
Pezzoli Gianni G
Brighina Laura L
Ferrarese Carlo C
Annesi Grazia G
Quattrone Andrea A
Gagliardi Monica M
Matsuo Hirotaka H
Nakayama Akiyoshi A
Hattori Nobutaka N
Nishioka Kenya K
Chung Sun Ju SJ
Kim Yun Joong YJ
Kolber Pierre P
van de Warrenburg Bart P C BPC
Bloem Bastiaan R BR
Aasly Jan J
Toft Mathias M
Pihlstrøm Lasse L
Guedes Leonor Correia LC
Ferreira Joaquim J JJ
Bardien Soraya S
Carr Jonathan J
Tolosa Eduardo E
Ezquerra Mario M
Pastor Pau P
Diez-Fairen Monica M
Wirdefeldt Karin K
Pedersen Nancy N
Ran Caroline C
Belin Andrea C AC
Puschmann Andreas A
Rödström Emil Ygland EY
Clarke Carl E CE
Morrison Karen E KE
Tan Manuela M
Krainc Dimitri D
Burbulla Lena F LF
Farrer Matt J MJ
Kruger Rejko R
Gasser Thomas T
Sharma Manu M
Truong Thérèse T
Elbaz Alexis A
Study Outcome
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