Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers
Authors: 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 ,   the EPITHYR consortium, Sreelatha Ashwin Ashok Kumar , Schulte Claudia , Grover Sandeep , May Patrick , Bobbili Dheeraj R. , 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. , Kruger Rejko , Gasser Thomas , Sharma Manu ,   the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage‐PD) consortium, Truong Thérèse , Elbaz Alexis 
Published: February 2023

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.