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Sugier, P.E.* ; Lucotte, E.A.* ; Domenighetti, C.* ; Law, M.H.* ; Iles, M.M.* ; Brown, K.* ; Amos, C.* ; McKay, J.D.* ; Hung, R.J.* ; Karimi, M.* ; Bacq-Daian, D.* ; Boland-Augé, A.* ; Olaso, R.* ; Deleuze, J.F.* ; Lesueur, F.* ; Ostroumova, E.* ; Kesminiene, A.* ; de Vathaire, F.* ; Guénel, P.* ; EPITHYR consortium* ; Sreelatha, A.A.K.* ; Schulte, C.* ; Grover, S.* ; May, P.* ; Bobbili, D.R.* ; Radivojkov-Blagojevic, M. ; Lichtner, P. ; Singleton, A.B.* ; Hernandez, D.G.* ; Edsall, C.* ; Mellick, G.D.* ; Zimprich, A.* ; Pirker, W.* ; Rogaeva, E.* ; Lang, A.E.* ; Kõks, S.* ; Taba, P.* ; Lesage, S.* ; Brice, A.* ; Corvol, J.C.* ; Chartier-Harlin, M.C.* ; Mutez, E.* ; Brockmann, K.* ; Deutschländer, A.B.* ; Hadjigeorgiou, G.M.* ; Dardiotis, E.* ; Stefanis, L.* ; Simitsi, A.M.* ; Valente, E.M.* ; Petrucci, S.* ; Straniero, L.* ; Zecchinelli, A.* ; Pezzoli, G.* ; Brighina, L.* ; Ferrarese, C.* ; Annesi, G.* ; Quattrone, A.* ; Gagliardi, M.* ; Matsuo, H.* ; Nakayama, A.* ; Hattori, N.* ; Nishioka, K.* ; Chung, S.J.* ; Kim, Y.J.* ; Kolber, P.* ; van de Warrenburg, B.P.C.* ; Bloem, B.R.* ; Aasly, J.* ; Toft, M.* ; Pihlstrøm, L.* ; Guedes, L.C.* ; Ferreira, J.J.* ; Bardien, S.* ; Carr, J.* ; Tolosa, E.* ; Ezquerra, M.* ; Pastor, P.* ; Diez-Fairen, M.* ; Wirdefeldt, K.* ; Pedersen, N.* ; Ran, C.* ; Belin, A.C.* ; Puschmann, A.* ; Rödström, E.Y.* ; Clarke, C.E.* ; Morrison, K.E.* ; Tan, M.* ; Krainc, D.* ; Burbulla, L.F.* ; Farrer, M.J.* ; Kruger, R.* ; Gasser, T.* ; Sharma, M.* ; Truong, T.* ; Elbaz, A.*

Investigation of shared genetic risk factors between parkinson's disease and cancers.

Mov. Disord. 38, 604-615 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Parkinson's Disease ; Cancer ; Genetic Correlation ; Pleiotropy ; Polygenic Risk Score; Susceptibility Loci; Cigarette-smoking; Lung-cancer; Association; Metaanalysis; Identification; Heterogeneity; Park2
ISSN (print) / ISBN 0885-3185
e-ISSN 1531-8257
Journal Movement Disorders
Quellenangaben Volume: 38, Issue: 4, Pages: 604-615 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
CF Genomics (CF-GEN)
Grants Pancreatic Cancer UK
CIHR
NHGRI NIH HHS
NHLBI NIH HHS
NCI NIH HHS
Cancer Research UK