Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers-Reference-Cited by-同舟云学术

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

Published:2023-02-14 Issue:4 Volume:38 Page:604-615
ISSN:0885-3185
Container-title:Movement Disorders
language:en
Short-container-title:Movement Disorders

Author:

Sugier Pierre‐Emmanuel¹²^ORCID,Lucotte Elise A.¹,Domenighetti Cloé¹^ORCID,Law Matthew H.³⁴,Iles Mark M.⁵,Brown Kevin⁶,Amos Christopher⁷,McKay James D.⁸,Hung Rayjean J.⁹¹⁰,Karimi Mojgan¹,Bacq‐Daian Delphine¹¹,Boland‐Augé Anne¹¹,Olaso Robert¹¹,Deleuze Jean‐françois¹¹,Lesueur Fabienne¹²,Ostroumova Evgenia⁸,Kesminiene Ausrele⁸,de Vathaire Florent¹³,Guénel Pascal¹,Sreelatha Ashwin Ashok Kumar¹⁴,Schulte Claudia¹⁵¹⁶^ORCID,Grover Sandeep¹⁴^ORCID,May Patrick¹⁷^ORCID,Bobbili Dheeraj R.¹⁷^ORCID,Radivojkov‐Blagojevic Milena¹⁸,Lichtner Peter¹⁸,Singleton Andrew B.¹⁹²⁰,Hernandez Dena G.¹⁹,Edsall Connor¹⁹,Mellick George D.²¹,Zimprich Alexander²²^ORCID,Pirker Walter²³,Rogaeva Ekaterina²⁴,Lang Anthony E.²⁵²⁶²⁷^ORCID,Koks Sulev²⁸²⁹,Taba Pille³⁰³¹,Lesage Suzanne³²,Brice Alexis³²,Corvol Jean‐Christophe³²³³^ORCID,Chartier‐Harlin Marie‐Christine³⁴,Mutez Eugénie³⁴^ORCID,Brockmann Kathrin¹⁵¹⁶^ORCID,Deutschländer Angela B.³⁵³⁶^ORCID,Hadjigeorgiou Georges M.³⁷³⁸³⁹,Dardiotis Efthimios³⁸,Stefanis Leonidas⁴⁰⁴¹^ORCID,Simitsi Athina Maria⁴⁰,Valente Enza Maria⁴²⁴³^ORCID,Petrucci Simona⁴⁴⁴⁵,Straniero Letizia⁴⁶,Zecchinelli Anna⁴⁷,Pezzoli Gianni⁴⁸,Brighina Laura⁴⁹⁵⁰,Ferrarese Carlo⁴⁹⁵⁰,Annesi Grazia⁵¹,Quattrone Andrea⁵²⁵³,Gagliardi Monica⁵³,Matsuo Hirotaka⁵⁴,Nakayama Akiyoshi⁵⁴,Hattori Nobutaka⁵⁵,Nishioka Kenya⁵⁵,Chung Sun Ju⁵⁶^ORCID,Kim Yun Joong⁵⁷,Kolber Pierre⁵⁸,van de Warrenburg Bart P.C.⁵⁹,Bloem Bastiaan R.⁵⁹,Aasly Jan⁶⁰,Toft Mathias⁶¹^ORCID,Pihlstrøm Lasse⁶¹,Guedes Leonor Correia⁶²⁶³,Ferreira Joaquim J.⁶²⁶³⁶⁴^ORCID,Bardien Soraya⁶⁵^ORCID,Carr Jonathan⁶⁶,Tolosa Eduardo⁶⁷⁶⁸^ORCID,Ezquerra Mario⁶⁹^ORCID,Pastor Pau⁷⁰,Diez‐Fairen Monica⁷¹⁷²,Wirdefeldt Karin⁷³⁷⁴,Pedersen Nancy⁷⁴,Ran Caroline⁷⁵,Belin Andrea C.⁷⁵,Puschmann Andreas⁷⁶,Rödström Emil Ygland⁷⁶,Clarke Carl E.⁷⁷,Morrison Karen E.⁷⁸,Tan Manuela⁶¹^ORCID,Krainc Dimitri⁷⁹,Burbulla Lena F.¹⁶⁷⁹⁸⁰⁸¹,Farrer Matt J.⁸²,Kruger Rejko¹⁷⁸³⁸⁴⁸⁵,Gasser Thomas¹⁵¹⁶,Sharma Manu¹⁴¹⁵^ORCID,Truong Thérèse¹,Elbaz Alexis¹^ORCID, ,

Affiliation:

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. Neurology Centre Hospitalier de Luxembourg Luxembourg Luxembourg

84. Parkinson's Research Clinic Centre Hospitalier de Luxembourg Luxembourg Luxembourg

85. Transversal Translational Medicine Luxembourg Institute of Health Strassen Luxembourg

Abstract

AbstractBackgroundEpidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties.ObjectiveWe used results from genome‐wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors.MethodsWe 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.ResultsWe confirmed a previously reported positive genetic correlation of PD with melanoma (Gcorr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (Gcorr = 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).ConclusionsWe 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.

Funder

Breast Cancer Research Foundation

Canadian Institutes of Health Research

Cancer Council Victoria

Cancer Research UK

EU Joint Programme – Neurodegenerative Disease Research

European Commission

FP7 Health

Government of Canada

Institut National de la Santé et de la Recherche Médicale

Institute of Cancer Research

Ligue Contre le Cancer