Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

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; Bobbili, Dheeraj Reddy; 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; Gasser, Thomas; Sharma, Manu; Landoulsi, Zied; consortium, Courage-PD; Truong, Thérèse; Elbaz, Ales

doi:10.1002/mds.29337

Available on ORBilu since
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.

2023 • In Movement Disorders, n/a (n/a)

Peer Reviewed verified by ORBi

Permalink
https://hdl.handle.net/10993/54595

DOI
10.1002/mds.29337

PubMed
36788297

Files Send to Details Statistics Bibliography Similar publications

Files

Full Text

Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers.pdf

Publisher postprint (16.4 MB)

All documents in ORBilu are protected by a user license.

Send to

RIS BibTex APA Chicago Permalink Twitter Linkedin

Details

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 :

Neurology
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

More authors (87 more)

External co-authors :

yes

Language :

English

Title :

Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

Publication date :

14 February 2023

Journal title :

Movement Disorders

ISSN :

1531-8257

Publisher :

John Wiley & Sons, Hoboken, United States - New York

Volume :

n/a

Issue :

n/a

Peer reviewed :

Peer Reviewed verified by ORBi

Focus Area :

Systems Biomedicine

Additional URL :

https://movementdisorders.onlinelibrary.wiley.com/doi/abs/10.1002/mds.29337

Funders :

JPND Courage-PD

Statistics

Number of views

38 (0 by Unilu)

Number of downloads

2 (0 by Unilu)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

WoS citations^™

Bibliography

Zhang X, Guarin D, Mohammadzadehhonarvar N, Chen X, Gao X. Parkinson's disease and cancer: a systematic review and meta-analysis of over 17 million participants. BMJ Open 2021;11(7):e046329.
Li X, Li W, Liu G, Shen X, Tang Y. Association between cigarette smoking and Parkinson's disease: a meta-analysis. Arch Gerontol Geriatr 2015;61(3):510–516.
Elbaz A, Peterson BJ, Yang P, et al. Nonfatal cancer preceding Parkinson's disease: a case-control study. Epidemiology 2002;13(2):157–164.
Driver JA, Kurth T, Buring JE, Gaziano JM, Logroscino G. Prospective case-control study of nonfatal cancer preceding the diagnosis of Parkinson's disease. Cancer Causes Control 2007;18(7):705–711.
Cui X, Liew Z, Hansen J, Lee PC, Arah OA, Ritz B. Cancers preceding Parkinson's disease after adjustment for bias in a Danish population-based case-control study. Neuroepidemiology 2019;52(3–4):136–143.
Hayes-Larson E, Shaw C, Ackley SF, et al. The role of dementia diagnostic delay in the inverse cancer-dementia association. J Gerontol, Ser A 2022;77(6):1254–1260.
Ospina-Romero M, Glymour MM, Hayes-Larson E, et al. Association between Alzheimer disease and cancer with evaluation of study biases: a systematic review and meta-analysis. JAMA Netw Open 2020;3(11):e2025515–e2025515.
Mencke P, Hanss Z, Boussaad I, Sugier PE, Elbaz A, Krüger R. Bidirectional relation between Parkinson's disease and glioblastoma multiforme. Front Neurol 2020;11:898.
Filippou PS, Outeiro TF. Cancer and Parkinson's disease: common targets, emerging hopes. Mov Disord 2021;36(2):340–346.
Moriarty N, Moriarty J. Highlighting the link between Parkinson's disease and malignant melanoma: a case report and literature review. Eur J Case Reports Intern Med 2019;6(11):1.
Inzelberg R, Flash S, Friedman E, Azizi E. Cutaneous malignant melanoma and Parkinson disease: common pathways? Ann Neurol 2016;80(6):811–820.
Jiang ZC, Chen XJ, Zhou Q, Gong XH, Chen X, Wu WJ. Downregulated LRRK2 gene expression inhibits proliferation and migration while promoting the apoptosis of thyroid cancer cells by inhibiting activation of the JNK signaling pathway. Int J Oncol 2019;55(1):21–34.
Xu L, Lin DC, Yin D, Koeffler HP. An emerging role of PARK2 in cancer. J Mol Med 2014;92(1):31–42.
Bartek J, Hodny Z. PARK2 orchestrates cyclins to avoid cancer. Nat Genet 2014;46(6):527–528.
Warø BJ, Aasly JO. Exploring cancer in LRRK2 mutation carriers and idiopathic Parkinson's disease. Brain Behav 2018;8(1):e00858.
Inzelberg R, Samuels Y, Azizi E, et al. Parkinson disease (PARK) genes are somatically mutated in cutaneous melanoma. Neurol Genet 2016;2(3):e70.
Devine MJ, Plun-Favreau H, Wood NW. Parkinson's disease and cancer: two wars, one front. Nat Rev Cancer 2011;11(11):812–823.
Senkevich K, Bandres-Ciga S, Yu E, Liyanage UE, Noyce AJ, Gan-Or Z. No evidence for a causal relationship between cancers and Parkinson's disease. J Parkinsons Dis 2021;11(2):801–809.
Dong J, Gao J, Nalls M, et al. Susceptibility loci for pigmentation and melanoma in relation to Parkinson's disease. Neurobiol Aging 2014;35(6):1512.e5–1512.e10.
Dube U, Ibanez L, Budde JP, et al. Overlapping genetic architecture between Parkinson disease and melanoma. Acta Neuropathol 2020;139(2):347–364.
Forés-martos J, Boullosa C, Rodrigo-domínguez D, et al. Transcriptomic and genetic associations between alzheimer's disease, parkinson's disease, and cancer. Cancers 2021;13(12):2990.
Domenighetti C, Sugier PE, Sreelatha AAK, et al. Mendelian randomisation study of smoking, alcohol, and coffee drinking in relation to Parkinson's disease. J Parkinsons Dis 2022;12(1):267–282.
Nalls MA, Blauwendraat C, Vallerga CL, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet Neurol 2019;18(12):1091–1102.
Blauwendraat C, Iwaki H, Makarious MB, et al. Investigation of autosomal genetic sex differences in Parkinson's disease. Ann Neurol 2021;90(1):35–42.
Michailidou K, Lindström S, Dennis J, et al. Association analysis identifies 65 new breast cancer risk loci. Nature 2017;551(7678):92–94.
Law MH, Bishop DT, Lee JE, et al. Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma. Nat Genet 2015;47(9):987–995.
Schumacher FR, Al Olama AA, Berndt SI, et al. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci. Nat Genet 2018;50(7):928–936.
McKay JD, Hung RJ, Han Y, et al. Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes. Nat Genet 2017;49(7):1126–1132.
Phelan CM, Kuchenbaecker KB, Tyrer JP, et al. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nat Genet 2017;49(5):680–691.
Truong T, Lesueur F, Sugier PE, et al. Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium. Int J Cancer 2021;148(12):2935–2946.
Bulik-Sullivan B, Finucane HK, Anttila V, et al. An atlas of genetic correlations across human diseases and traits. Nat Genet 2015;47(11):1236–1241.
Liyanarachchi S, Gudmundsson J, Ferkingstad E, et al. Assessing thyroid cancer risk using polygenic risk scores. Proc Natl Acad Sci U S A 2020;117(11):5997–6002.
Mavaddat N, Michailidou K, Dennis J, et al. Polygenic risk scores for prediction of breast cancer and breast cancer subtypes. Am J Hum Genet 2019;104(1):21–34.
Yang X, Leslie G, Gentry-Maharaj A, et al. Evaluation of polygenic risk scores for ovarian cancer risk prediction in a prospective cohort study. J Med Genet 2018;55(8):546–554.
König IR, Loley C, Erdmann J, Ziegler A. How to include chromosome X in your genome-wide association study. Genet Epidemiol 2014;38(2):97–103.
Gu F, Chen TH, Pfeiffer RM, et al. Combining common genetic variants and non-genetic risk factors to predict risk of cutaneous melanoma. Hum Mol Genet 2018;27(3):4145–4156.
Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21(11):1539–1558.
Johnson T. Efficient calculation for multi-SNP genetic risk scores. 2012.
Chang D, Nalls MA, Hallgrímsdóttir IB, et al. A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci. Nat Genet 2017;49(10):1511–1516.
Chen C, Zheng H, Hu Z. Association between Parkinson's disease and risk of prostate cancer in different populations: an updated meta-analysis. Sci Rep 2017;7(1):1–6.
Rashkin SR, Graff RE, Kachuri L, et al. Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts. Nat Commun 2020;11(1):1–14.
Khuder SA. Effect of cigarette smoking on major histological types of lung cancer: a meta-analysis. Lung Cancer 2001;31(2–3):139–148.