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 Brown, Christopher Amos, James D. McKay, Rayjean J. Hung, Mojgan Karimi, Delphine Bacq-Daian, Anne Boland-Augé, Robert Olaso, Jean françois Deleuze, Fabienne Lesueur, Evgenia Ostroumova, Ausrele Kesminiene, Florent de Vathaire, Pascal Guénel, Ashwin Ashok Kumar SreelathaClaudia Schulte, Sandeep Grover, Patrick May, Dheeraj R. Bobbili, Milena Radivojkov-Blagojevic, Peter Lichtner, Andrew B. Singleton, Dena G. Hernandez, Connor Edsall, George D. Mellick, Alexander Zimprich, Walter Pirker, Ekaterina Rogaeva, Anthony E. Lang, Sulev Koks, Pille Taba, Suzanne Lesage, Alexis Brice, Jean Christophe Corvol, Marie Christine Chartier-Harlin, Eugénie Mutez, Kathrin Brockmann, Angela B. Deutschländer, Georges M. Hadjigeorgiou, Efthimios Dardiotis, Leonidas Stefanis, Athina Maria Simitsi, Enza Maria Valente, Simona Petrucci, Rejko Kruger, the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage-PD) consortium, the EPITHYR consortium

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)604-615
Number of pages12
JournalMovement Disorders
Volume38
Issue number4
Early online date14 Feb 2023
DOIs
Publication statusPublished - Apr 2023

Keywords

  • cancer
  • genetic correlation
  • Parkinson's disease
  • pleiotropy
  • polygenic risk score

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