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

被引：12

作者：

Sugier, Pierre-Emmanuel ^{[1
,2
]}

Lucotte, Elise A. ^{[1
]}

Domenighetti, Cloe ^{[1
]}

Law, Matthew H. ^{[3
,4
]}

Iles, Mark M. ^{[5
]}

Brown, Kevin ^{[6
]}

Amos, Christopher ^{[7
]}

McKay, James D. ^{[8
]}

Hung, Rayjean J. ^{[9
,10
]}

Karimi, Mojgan ^{[1
]}

Bacq-Daian, Delphine ^{[11
]}

Boland-Auge, Anne ^{[11
]}

Olaso, Robert ^{[11
]}

Deleuze, Jean-francois ^{[11
]}

Lesueur, Fabienne ^{[12
]}

Ostroumova, Evgenia ^{[8
]}

Kesminiene, Ausrele ^{[8
]}

de Vathaire, Florent ^{[13
]}

Guenel, Pascal ^{[1
]}

Sreelatha, Ashwin Ashok Kumar ^{[14
]}

Schulte, Claudia ^{[15
,16
]}

Grover, Sandeep ^{[14
]}

May, Patrick ^{[17
]}

Bobbili, Dheeraj R. ^{[17
]}

Radivojkov-Blagojevic, Milena ^{[18
]}

Lichtner, Peter ^{[18
]}

Singleton, Andrew B. ^{[19
,20
]}

Hernandez, Dena G. ^{[19
]}

Edsall, Connor ^{[19
]}

Mellick, George D. ^{[21
]}

Zimprich, Alexander ^{[22
]}

Pirker, Walter ^{[23
]}

Rogaeva, Ekaterina ^{[24
]}

Lang, Anthony E. ^{[25
,26
,27
]}

Koks, Sulev ^{[28
,29
]}

Taba, Pille ^{[30
,31
]}

Lesage, Suzanne ^{[32
]}

Brice, Alexis ^{[32
]}

Corvol, Jean-Christophe ^{[32
,33
]}

Chartier-Harlin, Marie-Christine ^{[34
]}

Mutez, Eugenie ^{[34
]}

Brockmann, Kathrin ^{[15
,16
]}

Deutschlaender, Angela B. ^{[35
,36
]}

Hadjigeorgiou, Georges M. ^{[37
,38
,39
,40
]}

Dardiotis, Efthimios ^{[39
]}

Stefanis, Leonidas ^{[41
,42
]}

Simitsi, Athina Maria ^{[41
]}

Valente, Enza Maria ^{[43
,44
]}

Petrucci, Simona ^{[45
,46
]}

Straniero, Letizia ^{[47
]}

机构：

[1] Univ Paris Saclay, UVSQ, Inserm,CESP, Gustave Roussy,Team Exposome Heredity Canc & Hlth, Villejuif, France

[2] CNRS, Lab Mathemat & Leurs Applicat Pau, E2S UPPA, Pau, France

[3] QIMR Berghofer Med Res Inst, Stat Genet, Brisbane, Qld, Australia

[4] Queensland Univ Technol, Fac Hlth, Brisbane, Qld, Australia

[5] Univ Leeds, Leeds Inst Canc & Pathol, Sect Epidemiol & Biostat, Leeds, W Yorkshire, England

[6] NCI, NIH, Div Canc Epidemiol & Genet, Lab Translat Genom, Bethesda, MD USA

[7] Baylor Med Coll Med, Inst Clin & Translat Res, Houston, TX USA

[8] Int Agcy Res Canc, Lyon, France

[9] Sinai Hlth Syst, Lunenfeld Tanenbuaum Res Inst, Toronto, ON, Canada

[10] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada

[11] Univ Paris Saclay, Inst Biol Francois Jacob, Ctr Natl Rech Genom Humaine, CEA, Evry, France

[12] PSL Univ, Mines ParisTech, Inst Curie, Inserm,U900, Paris, France

[13] Univ Paris Saclay, UVSQ, Gustave Roussy, Inserm,Team Epidemiol Radiat,CESP, Villejuif, France

[14] Univ Tubingen, Inst Clin Epidemiol & Appl Biometry, Ctr Genet Epidemiol, Tubingen, Germany

[15] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany

[16] German Ctr Neurodegenerat Dis, Tubingen, Germany

[17] Univ Luxembourg, Luxembourg Ctr Syst Biomed, Translat Neurosci, Esch Belval, Luxembourg

[18] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany

[19] NIA, NIH, Mol Genet Sect, Neurogenet Lab, Bethesda, MD USA

[20] NIA, NIH, Ctr Alzheimers & Related Dementias, Bethesda, MD USA

[21] Griffith Univ, Griffith Inst Drug Discovery, Nathan, Qld, Australia

[22] Med Univ Vienna, Dept Neurol, Vienna, Austria

[23] Klin Ottakring, Dept Neurol, Vienna, Austria

[24] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada

[25] UHN, Toronto Western Hosp, Edmond J Safra Program Parkinsons Dis, Morton & Gloria Shulman Movement Disorders Clin, Toronto, ON, Canada

[26] Univ Toronto, Div Neurol, Toronto, ON, Canada

[27] Krembil Brain Inst, Toronto, ON, Canada

[28] Murdoch Univ, Ctr Mol Med & Innovat Therapeut, Murdoch, WA, Australia

[29] Perron Inst Neurol & Translat Sci, Nedlands, WA, Australia

[30] Univ Tartu, Dept Neurol & Neurosurg, Tartu, Estonia

[31] Tartu Univ Hosp, Neurol Clin, Tartu, Estonia

[32] Sorbonne Univ, Inst Cerveau Paris Brain Inst ICM, CNRS,INSERM, Dept Neurol,Assistance Publ Hop Paris, Paris, France

[33] Assistance Publ Hop Paris, CIC Neurosci, Dept Neurol, Paris, France

[34] Univ Lille, Ctr Rech Lille Neurosci & Cognit, Inserm, CHU Lille,UMR S 1172,LilCog, Lille, France

[35] Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany

[36] Max Planck Inst Psychiat, Dept Neurol, Munich, Germany

[37] Mayo Clin Florida, Dept Neurol, Jacksonville, FL USA

[38] Mayo Clin Florida, Dept Clin Gen, Jacksonville, FL USA

[39] Univ Thessaly, Univ Hosp Larissa, Dept Neurol, Neurogenet Lab, Larisa, Greece

[40] Univ Cyprus, Sch Med, Dept Neurol, Nicosia, Cyprus

[41] Natl & Kapodistrian Univ Athens, Sch Med, Eginit Hosp, Dept Neurol 1, Athens, Greece

[42] Biomed Res Fdn Acad Athens, Ctr Clin Res Expt Surg & Translat Res, Athens, Greece

[43] Univ Pavia, Dept Mol Med, Pavia, Italy

[44] Ist Ricovero & Cura Carattere Sci IRCCS Mondino F, Pavia, Italy

[45] S Andrea Univ Hosp, UOC Med Genet & Adv Cell Diagnost, Rome, Italy

[46] Sapienza Univ Rome, Dept Clin & Mol Med, Rome, Italy

[47] Humanitas Univ, Dept Biomed Sci, Milan, Italy

[48] Azienda Socio Sanit Terr ASST Gaetano, Parkinson Inst, CTO, Milan, Italy

[49] Fontaz Grigioni, Parkinson Inst, Via Zuretti, Milan, Italy

[50] San Gerardo Hosp, Dept Neurol, Monza, Italy

来源：

MOVEMENT DISORDERS | 2023年 / 38卷 / 04期

基金：

美国国家卫生研究院; 英国医学研究理事会; 加拿大健康研究院; 欧盟地平线“2020”;

关键词：

Parkinson's disease; cancer; genetic correlation; polygenic risk score; pleiotropy; SUSCEPTIBILITY LOCI; CIGARETTE-SMOKING; LUNG-CANCER; ASSOCIATION; METAANALYSIS; IDENTIFICATION; HETEROGENEITY; PARK2;

D O I：

10.1002/mds.29337

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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 (G(corr) = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (G(corr) = 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. (c) 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.

引用

页码：604 / 615

页数：12

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