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 Sreelatha; Claudia 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; Karen E. Morrison; the EPITHYR consortium; the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage‐PD) consortium

doi:10.1002/mds.29337

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, Karen E. Morrison, the EPITHYR consortium, the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage‐PD) consortium

^*Corresponding author for this work

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Journal	Movement Disorders
Early online date	14 Feb 2023
DOIs	https://doi.org/10.1002/mds.29337
Publication status	Early online date - 14 Feb 2023

Keywords

RESEARCH ARTICLE
RESEARCH ARTICLES
Parkinson's disease
cancer
genetic correlation
polygenic risk score
pleiotropy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Investigation of shared genetic risk factors between Parkinson's disease and cancers
Copyright 2023 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
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Cite this

Sugier, PE., 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., Lesueur, F., Ostroumova, E., Kesminiene, A., de Vathaire, F., Guénel, P., ... the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage‐PD) consortium (2023). Investigation of shared genetic risk factors between Parkinson's disease and cancers. Movement Disorders. Advance online publication. https://doi.org/10.1002/mds.29337

@article{3be85d88fad14b2fb82c54220d808994,

title = "Investigation of shared genetic risk factors between Parkinson's disease and cancers",

abstract = "BackgroundEpidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties.ObjectiveWe used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors.MethodsWe 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.ResultsWe 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).ConclusionsWe show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. {\textcopyright} 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.",

keywords = "RESEARCH ARTICLE, RESEARCH ARTICLES, Parkinson's disease, cancer, genetic correlation, polygenic risk score, pleiotropy",

author = "Pierre‐Emmanuel Sugier and Lucotte, {Elise A.} and Clo{\'e} Domenighetti and Law, {Matthew H.} and Iles, {Mark M.} and Kevin Brown and Christopher Amos and McKay, {James D.} and Hung, {Rayjean J.} and Mojgan Karimi and Delphine Bacq‐Daian and Anne Boland‐Aug{\'e} and Robert Olaso and Jean‐fran{\c c}ois Deleuze and Fabienne Lesueur and Evgenia Ostroumova and Ausrele Kesminiene and {de Vathaire}, Florent and Pascal Gu{\'e}nel and Sreelatha, {Ashwin Ashok Kumar} and Claudia Schulte and Sandeep Grover and Patrick May and Bobbili, {Dheeraj R.} and Milena Radivojkov‐Blagojevic and Peter Lichtner and Singleton, {Andrew B.} and Hernandez, {Dena G.} and Connor Edsall and Mellick, {George D.} and Alexander Zimprich and Walter Pirker and Ekaterina Rogaeva and Lang, {Anthony E.} and Sulev Koks and Pille Taba and Suzanne Lesage and Alexis Brice and Jean‐Christophe Corvol and Marie‐Christine Chartier‐Harlin and Eug{\'e}nie Mutez and Kathrin Brockmann and Deutschl{\"a}nder, {Angela B.} and Hadjigeorgiou, {Georges M.} and Efthimios Dardiotis and Leonidas Stefanis and Simitsi, {Athina Maria} and Valente, {Enza Maria} and Simona Petrucci and Morrison, {Karen E.} and {the EPITHYR consortium} and {the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage‐PD) consortium}",

year = "2023",

month = feb,

day = "14",

doi = "10.1002/mds.29337",

language = "English",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "John Wiley & Sons Inc.",

}

Sugier, PE, Lucotte, EA, Domenighetti, C, Law, MH, Iles, MM, Brown, K, Amos, C, McKay, JD, Hung, RJ, Karimi, M, Bacq‐Daian, D, Boland‐Augé, A, Olaso, R, Deleuze, J, Lesueur, F, Ostroumova, E, Kesminiene, A, de Vathaire, F, Guénel, P, Sreelatha, AAK, Schulte, C, Grover, S, May, P, Bobbili, DR, Radivojkov‐Blagojevic, M, Lichtner, P, Singleton, AB, Hernandez, DG, Edsall, C, Mellick, GD, Zimprich, A, Pirker, W, Rogaeva, E, Lang, AE, Koks, S, Taba, P, Lesage, S, Brice, A, Corvol, JC, Chartier‐Harlin, MC, Mutez, E, Brockmann, K, Deutschländer, AB, Hadjigeorgiou, GM, Dardiotis, E, Stefanis, L, Simitsi, AM, Valente, EM, Petrucci, S, Morrison, KE, the EPITHYR consortium & the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage‐PD) consortium 2023, 'Investigation of shared genetic risk factors between Parkinson's disease and cancers', Movement Disorders. https://doi.org/10.1002/mds.29337

TY - JOUR

T1 - Investigation of shared genetic risk factors between Parkinson's disease and cancers

AU - Sugier, Pierre‐Emmanuel

AU - Lucotte, Elise A.

AU - Domenighetti, Cloé

AU - Law, Matthew H.

AU - Iles, Mark M.

AU - Brown, Kevin

AU - Amos, Christopher

AU - McKay, James D.

AU - Hung, Rayjean J.

AU - Karimi, Mojgan

AU - Bacq‐Daian, Delphine

AU - Boland‐Augé, Anne

AU - Olaso, Robert

AU - Deleuze, Jean‐françois

AU - Lesueur, Fabienne

AU - Ostroumova, Evgenia

AU - Kesminiene, Ausrele

AU - de Vathaire, Florent

AU - Guénel, Pascal

AU - Sreelatha, Ashwin Ashok Kumar

AU - Schulte, Claudia

AU - Grover, Sandeep

AU - May, Patrick

AU - Bobbili, Dheeraj R.

AU - Radivojkov‐Blagojevic, Milena

AU - Lichtner, Peter

AU - Singleton, Andrew B.

AU - Hernandez, Dena G.

AU - Edsall, Connor

AU - Mellick, George D.

AU - Zimprich, Alexander

AU - Pirker, Walter

AU - Rogaeva, Ekaterina

AU - Lang, Anthony E.

AU - Koks, Sulev

AU - Taba, Pille

AU - Lesage, Suzanne

AU - Brice, Alexis

AU - Corvol, Jean‐Christophe

AU - Chartier‐Harlin, Marie‐Christine

AU - Mutez, Eugénie

AU - Brockmann, Kathrin

AU - Deutschländer, Angela B.

AU - Hadjigeorgiou, Georges M.

AU - Dardiotis, Efthimios

AU - Stefanis, Leonidas

AU - Simitsi, Athina Maria

AU - Valente, Enza Maria

AU - Petrucci, Simona

AU - Morrison, Karen E.

AU - the EPITHYR consortium

AU - the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage‐PD) consortium

PY - 2023/2/14

Y1 - 2023/2/14

N2 - BackgroundEpidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties.ObjectiveWe used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors.MethodsWe 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.ResultsWe 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).ConclusionsWe 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.

AB - BackgroundEpidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties.ObjectiveWe used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors.MethodsWe 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.ResultsWe 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).ConclusionsWe 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.

KW - RESEARCH ARTICLE

KW - RESEARCH ARTICLES

KW - Parkinson's disease

KW - cancer

KW - genetic correlation

KW - polygenic risk score

KW - pleiotropy

U2 - 10.1002/mds.29337

DO - 10.1002/mds.29337

M3 - Article

SN - 0885-3185

JO - Movement Disorders

JF - Movement Disorders

ER -

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

Abstract

Keywords

UN SDGs

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