Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

Pierre-Emmanuel Sugier^{1

2}, Elise A Lucotte¹, Cloé Domenighetti¹, Matthew H Law^{3

4}, Mark M Iles⁵, Kevin Brown⁶, Christopher Amos⁷, James D McKay⁸, Rayjean J Hung^{9

10}, Mojgan Karimi¹, Delphine Bacq-Daian¹¹, Anne Boland-Augé¹¹, Robert Olaso¹¹, Jean-François Deleuze¹¹, Fabienne Lesueur¹², Evgenia Ostroumova⁸, Ausrele Kesminiene⁸, Florent de Vathaire¹³, Pascal Guénel¹; EPITHYR consortium; Ashwin Ashok Kumar Sreelatha¹⁴, Claudia Schulte^{15

16}, Sandeep Grover¹⁴, Patrick May¹⁷, Dheeraj R Bobbili¹⁷, Milena Radivojkov-Blagojevic¹⁸, Peter Lichtner¹⁸, Andrew B Singleton^{19

20}, Dena G Hernandez¹⁹, Connor Edsall¹⁹, George D Mellick²¹, Alexander Zimprich²², Walter Pirker²³, Ekaterina Rogaeva²⁴, Anthony E Lang^{25

26

27}, Sulev Koks^{28

29}, Pille Taba^{30

31}, Suzanne Lesage³², Alexis Brice³², Jean-Christophe Corvol^{32

33}, Marie-Christine Chartier-Harlin³⁴, Eugénie Mutez³⁴, Kathrin Brockmann^{15

16}, Angela B Deutschländer^{35

36}, Georges M Hadjigeorgiou^{37

38

39}, Efthimios Dardiotis³⁸, Leonidas Stefanis^{40

41}, Athina Maria Simitsi⁴⁰, Enza Maria Valente^{42

43}, Simona Petrucci^{44

45}, Letizia Straniero⁴⁶, Anna Zecchinelli⁴⁷, Gianni Pezzoli⁴⁸, Laura Brighina^{49

50}, Carlo Ferrarese^{49

50}, Grazia Annesi⁵¹, Andrea Quattrone^{52

53}, Monica Gagliardi⁵³, Hirotaka Matsuo⁵⁴, Akiyoshi Nakayama⁵⁴, Nobutaka Hattori⁵⁵, Kenya Nishioka⁵⁵, Sun Ju Chung⁵⁶, Yun Joong Kim⁵⁷, Pierre Kolber⁵⁸, Bart P C van de Warrenburg⁵⁹, Bastiaan R Bloem⁵⁹, Jan Aasly⁶⁰, Mathias Toft⁶¹, Lasse Pihlstrøm⁶¹, Leonor Correia Guedes^{62

63}, Joaquim J Ferreira^{62

63

64}, Soraya Bardien⁶⁵, Jonathan Carr⁶⁶, Eduardo Tolosa^{67

68}, Mario Ezquerra⁶⁹, Pau Pastor⁷⁰, Monica Diez-Fairen^{71

72}, Karin Wirdefeldt^{73

74}, Nancy Pedersen⁷⁴, Caroline Ran⁷⁵, Andrea C Belin⁷⁵, Andreas Puschmann⁷⁶, Emil Ygland Rödström⁷⁶, Carl E Clarke⁷⁷, Karen E Morrison⁷⁸, Manuela Tan⁶¹, Dimitri Krainc⁷⁹, Lena F Burbulla^{16

79

80

81}, Matt J Farrer⁸², Rejko Kruger^{17

58

83

84}, Thomas Gasser^{15

16}, Manu Sharma^{14

15}; Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage-PD) consortium; Thérèse Truong¹, Alexis Elbaz¹

Affiliations

¹ Université Paris-Saclay, UVSQ, Inserm, Gustave Roussy, Team "Exposome, Heredity, Cancer and Health", CESP, Villejuif, France.
² Laboratoire de Mathématiques et de leurs Applications de Pau, E2S UPPA, CNRS, Pau, France.
³ Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
⁴ Faculty of Health, Queensland University of Technology, Brisbane, Australia.
⁵ Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
⁶ Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
⁷ Institute for Clinical and Translational Research, Baylor Medical College of Medecine, Houston, Texas, USA.
⁸ International Agency for Research on Cancer, Lyon, France.
⁹ Lunenfeld-Tanenbuaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
¹⁰ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
¹¹ Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, Institut de Biologie François Jacob, Evry, France.
¹² Inserm, U900, Institut Curie, PSL University, Mines ParisTech, Paris, France.
¹³ Université Paris-Saclay, UVSQ, Gustave Roussy, Inserm, Team "Epidemiology of radiations," CESP, Villejuif, France.
¹⁴ Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Tübingen, Germany.
¹⁵ Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tubingen, Tübingen, Germany.
¹⁶ German Center for Neurodegenerative Diseases, Tübingen, Germany.
¹⁷ Translational Neuroscience, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-Belval, Luxembourg.
¹⁸ Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
¹⁹ Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
²⁰ Center For Alzheimer's and Related Dementias, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
²¹ Griffith Institute for Drug Discovery, Griffith University, Nathan, Australia.
²² Department of Neurology, Medical University of Vienna, Vienna, Austria.
²³ Department of Neurology, Klinik Ottakring, Vienna, Austria.
²⁴ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
²⁵ Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada.
²⁶ Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
²⁷ Krembil Brain Institute, Toronto, Ontario, Canada.
²⁸ Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, Australia.
²⁹ Perron Institute for Neurological and Translational Science, Nedlands, Australia.
³⁰ Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
³¹ Neurology Clinic, Tartu University Hospital, Tartu, Estonia.
³² Department of Neurology, Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, INSERM, CNRS, Assistance Publique Hôpitaux de Paris, Paris, France.
³³ Assistance Publique Hôpitaux de Paris, Department of Neurology, CIC Neurosciences, Paris, France.
³⁴ Université de Lille, Inserm, CHU Lille, UMR-S 1172, LilNCog, Centre de Recherche Lille Neurosciences & Cognition, Lille, France.
³⁵ Department of Neurology, Ludwig Maximilians University of Munich, Munich, Germany.
³⁶ Department of Neurology, Max Planck Institute of Psychiatry, Munich, Germany.
³⁷ Department of Neurology and Department of Clinical Genomics, Mayo Clinic Florida, Jacksonville, Florida, USA.
³⁸ Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
³⁹ Department of Neurology, Medical School, University of Cyprus, Nicosia, Cyprus.
⁴⁰ 1st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
⁴¹ Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
⁴² Department of Molecular Medicine, University of Pavia, Pavia, Italy.
⁴³ Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation, Pavia, Italy.
⁴⁴ UOC Medical Genetics and Advanced Cell Diagnostics, S. Andrea University Hospital, Rome, Italy.
⁴⁵ Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
⁴⁶ Department of Biomedical Sciences, Humanitas University, Milan, Italy.
⁴⁷ Parkinson Institute, Azienda Socio Sanitaria Territoriale (ASST) Gaetano Pini/CTO, Milan, Italy.
⁴⁸ Parkinson Institute, Fontazione Grigioni-Via Zuretti, Milan, Italy.
⁴⁹ Department of Neurology, San Gerardo Hospital, Monza, Italy.
⁵⁰ Department of Medicine and Surgery and Milan Center for Neuroscience, University of Milano Bicocca, Milan, Italy.
⁵¹ Institute for Biomedical Research and Innovation, National Research Council, Cosenza, Italy.
⁵² Institute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy.
⁵³ Department of Medical and Surgical Sciences, Neuroscience Research Center, Magna Graecia University, Catanzaro, Italy.
⁵⁴ Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama, Japan.
⁵⁵ Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
⁵⁶ Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁵⁷ Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.
⁵⁸ Neurology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
⁵⁹ Department of Neurology, Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands.
⁶⁰ Department of Neurology, St. Olav's Hospital and Norwegian University of Science and Technology, Trondheim, Norway.
⁶¹ Department of Neurology, Oslo University Hospital, Oslo, Norway.
⁶² Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
⁶³ Department of Neurosciences and Mental Health, Neurology, Hospital de Santa Maria, Centro Hospitalar Universitario Lisboa Norte (CHULN), Lisbon, Portugal.
⁶⁴ Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
⁶⁵ Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
⁶⁶ Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
⁶⁷ 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.
⁶⁸ Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED: CB06/05/0018-ISCIII), Barcelona, Spain.
⁶⁹ 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.
⁷⁰ Unit of Neurodegenerative Diseases, Department of Neurology, University Hospital Germans Trias i Pujol, Barcelona, Spain.
⁷¹ Fundació per la Recerca Biomèdica i Social Mútua Terrassa, Barcelona, Spain.
⁷² Movement Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Barcelona, Spain.
⁷³ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁷⁴ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁷⁵ Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁷⁶ Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Neurology, Lund, Sweden.
⁷⁷ University of Birmingham and Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom.
⁷⁸ Faculty of Medicine, Health and Life Sciences, Queens University, Belfast, United Kingdom.
⁷⁹ Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
⁸⁰ Metabolic Biochemistry, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
⁸¹ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
⁸² Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA.
⁸³ Parkinson's Research Clinic, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
⁸⁴ Transversal Translational Medicine, Luxembourg Institute of Health, Strassen, Luxembourg.

PMID: 36788297
PMCID: PMC10334300
DOI: 10.1002/mds.29337

Meta-Analysis

Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

Pierre-Emmanuel Sugier et al. Mov Disord. 2023 Apr.

. 2023 Apr;38(4):604-615.

doi: 10.1002/mds.29337. Epub 2023 Feb 14.

Authors

Affiliations

¹ Université Paris-Saclay, UVSQ, Inserm, Gustave Roussy, Team "Exposome, Heredity, Cancer and Health", CESP, Villejuif, France.
² Laboratoire de Mathématiques et de leurs Applications de Pau, E2S UPPA, CNRS, Pau, France.
³ Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
⁴ Faculty of Health, Queensland University of Technology, Brisbane, Australia.
⁵ Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
⁶ Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
⁷ Institute for Clinical and Translational Research, Baylor Medical College of Medecine, Houston, Texas, USA.
⁸ International Agency for Research on Cancer, Lyon, France.
⁹ Lunenfeld-Tanenbuaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
¹⁰ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
¹¹ Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, Institut de Biologie François Jacob, Evry, France.
¹² Inserm, U900, Institut Curie, PSL University, Mines ParisTech, Paris, France.
¹³ Université Paris-Saclay, UVSQ, Gustave Roussy, Inserm, Team "Epidemiology of radiations," CESP, Villejuif, France.
¹⁴ Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tubingen, Tübingen, Germany.
¹⁵ Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tubingen, Tübingen, Germany.
¹⁶ German Center for Neurodegenerative Diseases, Tübingen, Germany.
¹⁷ Translational Neuroscience, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-Belval, Luxembourg.
¹⁸ Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
¹⁹ Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
²⁰ Center For Alzheimer's and Related Dementias, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
²¹ Griffith Institute for Drug Discovery, Griffith University, Nathan, Australia.
²² Department of Neurology, Medical University of Vienna, Vienna, Austria.
²³ Department of Neurology, Klinik Ottakring, Vienna, Austria.
²⁴ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
²⁵ Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada.
²⁶ Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
²⁷ Krembil Brain Institute, Toronto, Ontario, Canada.
²⁸ Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, Australia.
²⁹ Perron Institute for Neurological and Translational Science, Nedlands, Australia.
³⁰ Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia.
³¹ Neurology Clinic, Tartu University Hospital, Tartu, Estonia.
³² Department of Neurology, Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, INSERM, CNRS, Assistance Publique Hôpitaux de Paris, Paris, France.
³³ Assistance Publique Hôpitaux de Paris, Department of Neurology, CIC Neurosciences, Paris, France.
³⁴ Université de Lille, Inserm, CHU Lille, UMR-S 1172, LilNCog, Centre de Recherche Lille Neurosciences & Cognition, Lille, France.
³⁵ Department of Neurology, Ludwig Maximilians University of Munich, Munich, Germany.
³⁶ Department of Neurology, Max Planck Institute of Psychiatry, Munich, Germany.
³⁷ Department of Neurology and Department of Clinical Genomics, Mayo Clinic Florida, Jacksonville, Florida, USA.
³⁸ Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
³⁹ Department of Neurology, Medical School, University of Cyprus, Nicosia, Cyprus.
⁴⁰ 1st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
⁴¹ Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
⁴² Department of Molecular Medicine, University of Pavia, Pavia, Italy.
⁴³ Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation, Pavia, Italy.
⁴⁴ UOC Medical Genetics and Advanced Cell Diagnostics, S. Andrea University Hospital, Rome, Italy.
⁴⁵ Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
⁴⁶ Department of Biomedical Sciences, Humanitas University, Milan, Italy.
⁴⁷ Parkinson Institute, Azienda Socio Sanitaria Territoriale (ASST) Gaetano Pini/CTO, Milan, Italy.
⁴⁸ Parkinson Institute, Fontazione Grigioni-Via Zuretti, Milan, Italy.
⁴⁹ Department of Neurology, San Gerardo Hospital, Monza, Italy.
⁵⁰ Department of Medicine and Surgery and Milan Center for Neuroscience, University of Milano Bicocca, Milan, Italy.
⁵¹ Institute for Biomedical Research and Innovation, National Research Council, Cosenza, Italy.
⁵² Institute of Neurology, Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy.
⁵³ Department of Medical and Surgical Sciences, Neuroscience Research Center, Magna Graecia University, Catanzaro, Italy.
⁵⁴ Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Saitama, Japan.
⁵⁵ Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
⁵⁶ Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
⁵⁷ Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.
⁵⁸ Neurology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
⁵⁹ Department of Neurology, Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands.
⁶⁰ Department of Neurology, St. Olav's Hospital and Norwegian University of Science and Technology, Trondheim, Norway.
⁶¹ Department of Neurology, Oslo University Hospital, Oslo, Norway.
⁶² Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
⁶³ Department of Neurosciences and Mental Health, Neurology, Hospital de Santa Maria, Centro Hospitalar Universitario Lisboa Norte (CHULN), Lisbon, Portugal.
⁶⁴ Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
⁶⁵ Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
⁶⁶ Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
⁶⁷ 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.
⁶⁸ Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED: CB06/05/0018-ISCIII), Barcelona, Spain.
⁶⁹ 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.
⁷⁰ Unit of Neurodegenerative Diseases, Department of Neurology, University Hospital Germans Trias i Pujol, Barcelona, Spain.
⁷¹ Fundació per la Recerca Biomèdica i Social Mútua Terrassa, Barcelona, Spain.
⁷² Movement Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Barcelona, Spain.
⁷³ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁷⁴ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁷⁵ Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁷⁶ Lund University, Skåne University Hospital, Department of Clinical Sciences Lund, Neurology, Lund, Sweden.
⁷⁷ University of Birmingham and Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom.
⁷⁸ Faculty of Medicine, Health and Life Sciences, Queens University, Belfast, United Kingdom.
⁷⁹ Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
⁸⁰ Metabolic Biochemistry, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
⁸¹ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
⁸² Department of Neurology, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA.
⁸³ Parkinson's Research Clinic, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.
⁸⁴ Transversal Translational Medicine, Luxembourg Institute of Health, Strassen, Luxembourg.

PMID: 36788297
PMCID: PMC10334300
DOI: 10.1002/mds.29337

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: We confirmed a previously reported positive genetic correlation of PD with melanoma (G_corr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (G_corr = 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).

Conclusions: 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.

Keywords: Parkinson's disease; cancer; genetic correlation; pleiotropy; polygenic risk score.

© 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.

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Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

Affiliations

Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

Authors

Affiliations

Abstract

References

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Grants and funding

LinkOut - more resources

Full Text Sources

Medical