Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers
Pierre‐Emmanuel Sugier, Elise A. Lucotte, Cloé Domenighetti, Matthew H. Law, Mark M. Iles, Kevin M. Brown, Christopher I. Amos, James McKay, Rayjean J. Hung, Mojgan Karimi, Delphine Bacq‐Daian, Anne Boland, Robert Olaso, Jean‐François Deleuze, Fabienne Lesueur, Evgenia Ostroumova, Ausrele Kesminiene, Florent de Vathaire, Pascal Guénel, Ashwin Ashok Kumar Sreelatha, Claudia Schulte, Sandeep Grover, Patrick May, Dheeraj Reddy Bobbili, Milena Radivojkov‐Blagojevic, Peter Lichtner, Andrew Singleton, Dena G. Hernandez, Connor Edsall, George D. Mellick, Alexander Zimprich, Walter Pirker, Ekaterina Rogaeva, Anthony E. Lang, Sulev Kõks, Pille Taba, Suzanne Lesage, Alexis Brice, Jean‐Christophe Corvol, Marie‐Christine Chartier‐Harlin, Eugénie Mutez, Kathrin Brockmann, Angela Deutschländer, G. Hadjigeorgiou, Efthimios Dardiotis, Leonidas Stefanis, Athina Maria Simitsi, Enza Maria Valente, Simona Petrucci, Letizia Straniero, Anna Zecchinelli, Gianni Pezzoli, Laura Brighina, Carlo Ferrarese, Grazia Annesi, Andrea Quattrone, Monica Gagliardi, Hirotaka Matsuo, Akiyoshi Nakayama, Nobutaka Hattori, Kenya Nishioka, Sun Ju Chung, Yun Joong Kim, Pierre Kolber, Bart P.C. van de Warrenburg, Bastiaan R. Bloem, Jan Aasly, Mathias Toft, Lasse Pihlstrøm, Leonor Correia Guedes, Joaquim J. Ferreira, Soraya Bardien, Jonathan Carr, Eduardo Tolosa, Mario Ezquerra, Pau Pástor, Mónica Díez-Fairén, Karin Wirdefeldt, Nancy L. Pedersen, Caroline Ran, Andrea Carmine Belin, Andreas Puschmann, Emil Ygland, Carl E Clarke, Karen Morrison, Manuela Tan, Dimitri Krainc, Lena F. Burbulla, Matthew J. Farrer, Rejko Krüger, Thomas Gasser, Manu Sharma, Thérèse Truong, Alexis Elbaz
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: = 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.