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18 March 2023
Article (Scientific journals)
Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers
Sugier, Pierre-Emmanuel; Lucotte, Elise A.; Domenighetti, Cloé et al.
2023In Movement Disorders, n/a (n/a)
Peer Reviewed verified by ORBi


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Keywords :
Parkinson's disease; cancer; genetic correlation; polygenic risk score; pleiotropy
Abstract :
[en] 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 (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). 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.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
- Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group)
Disciplines :
Genetics & genetic processes
Author, co-author :
Sugier, Pierre-Emmanuel
Lucotte, Elise A.
Domenighetti, Cloé
Law, Matthew H.
Iles, Mark M.
Brown, Kevin
Amos, Christopher
McKay, James D.
Hung, Rayjean J.
Karimi, Mojgan
Bacq-Daian, Delphine
Boland-Augé, Anne
Olaso, Robert
Deleuze, Jean-François
Lesueur, Fabienne
Ostroumova, Evgenia
Kesminiene, Ausrele
de Vathaire, Florent
Guénel, Pascal
consortium, The Epithyr
Sreelatha, Ashwin Ashok Kumar
Schulte, Claudia
Grover, Sandeep
May, Patrick ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Bobbili, Dheeraj Reddy ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Radivojkov-Blagojevic, Milena
Lichtner, Peter
Singleton, Andrew B.
Hernandez, Dena G.
Edsall, Connor
Mellick, George D.
Zimprich, Alexander
Pirker, Walter
Rogaeva, Ekaterina
Lang, Anthony E.
Koks, Sulev
Taba, Pille
Lesage, Suzanne
Brice, Alexis
Corvol, Jean-Christophe
Chartier-Harlin, Marie-Christine
Mutez, Eugénie
Brockmann, Kathrin
Deutschländer, Angela B.
Hadjigeorgiou, Georges M.
Dardiotis, Efthimios
Stefanis, Leonidas
Simitsi, Athina Maria
Valente, Enza Maria
Petrucci, Simona
Straniero, Letizia
Zecchinelli, Anna
Pezzoli, Gianni
Brighina, Laura
Ferrarese, Carlo
Annesi, Grazia
Quattrone, Andrea
Gagliardi, Monica
Matsuo, Hirotaka
Nakayama, Akiyoshi
Hattori, Nobutaka
Nishioka, Kenya
Chung, Sun Ju
Kim, Yun Joong
Kolber, Pierre
van de Warrenburg, Bart P. C.
Bloem, Bastiaan R.
Aasly, Jan
Toft, Mathias
Pihlstrøm, Lasse
Guedes, Leonor Correia
Ferreira, Joaquim J.
Bardien, Soraya
Carr, Jonathan
Tolosa, Eduardo
Ezquerra, Mario
Pastor, Pau
Diez-Fairen, Monica
Wirdefeldt, Karin
Pedersen, Nancy
Ran, Caroline
Belin, Andrea C.
Puschmann, Andreas
Rödström, Emil Ygland
Clarke, Carl E.
Morrison, Karen E.
Tan, Manuela
Krainc, Dimitri
Burbulla, Lena F.
Farrer, Matt J.
Krüger, Rejko ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
Gasser, Thomas
Sharma, Manu
Landoulsi, Zied ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
consortium, Courage-PD
Truong, Thérèse
Elbaz, Ales
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Title :
Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers
Publication date :
14 February 2023
Journal title :
Movement Disorders
Publisher :
John Wiley & Sons, Hoboken, United States - New York
Volume :
Issue :
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
Funders :
JPND Courage-PD


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