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 - Kruger, Rejko
AU - the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (Courage-PD) consortium
AU - the EPITHYR consortium
N1 - Funding Information:
We would also like to thank the following for funding support: Institute of Cancer Research and the Everyman Campaign, the Prostate Cancer Research Foundation, Prostate Research Campaign UK (now PCUK), the Orchid Cancer Appeal, Rosetrees Trust, the National Cancer Research Network UK, and the National Cancer Research Institute (NCRI) UK. We are grateful for support of NIHR funding to the NIHR Biomedical Research Centre at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust.
Funding Information:
The EPITHYR genome‐wide association analyses were supported by Institut National du Cancer (9533) and Fondation ARC (PGA120150202302). The breast cancer genome‐wide association analyses were supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the “Ministère de l'Économie, de la Science et de l'Innovation du Québec” through Genome Québec and grant PSR‐SIIRI‐701, the National Institutes of Health (U19 CA148065 and X01HG007492), Cancer Research UK (C1287/A10118, C1287/A16563, and C1287/A10710), and The European Union (HEALTH‐F2‐2009‐223175 and H2020 633784 and 634935). All studies and funders are listed in Michailidou et al. 25
Funding Information:
The prostate cancer genome‐wide association analyses are supported by the Canadian Institutes of Health Research, European Commission's Seventh Framework Programme grant agreement no. 223175 (HEALTH‐F2‐2009‐223175), Cancer Research UK grants (C5047/A7357, C1287/A10118, C1287/A16563, C5047/A3354, C5047/A10692, and C16913/A6135), and the National Institute of Health (NIH) Cancer Post‐Cancer genome‐wide association study (GWAS) initiative grant 1U19 CA 148537–01 (the GAME‐ON initiative).
Funding Information:
P.‐E.S. received a postdoctoral grant from the patient group. This project received financial support from INSERM Cancer and the “Ligue contre le Cancer”. C.D. is the recipient of a doctoral grant from Université Paris‐Saclay, France. This study used data from the Courage‐PD consortium, conducted under a partnership agreement between 35 studies. The Courage‐PD consortium is supported by the EU Joint Program for Neurodegenerative Disease research (JPND; https://www.neurodegenerationresearch.eu/initiatives/annual-calls-for-proposals/closed-calls/risk-factors-2012/risk-factor-call-results/courage-pd/ ). France Parkinson
Funding Information:
The Prostate Cancer Program of Cancer Council Victoria also acknowledges grant support from the National Health and Medical Research Council, Australia (126402, 209057, 251533, 396414, 450104, 504700, 504702, 504715, 623204, 940394, and 614,296), VicHealth, Cancer Council Victoria, Prostate Cancer Foundation of Australia, Whitten Foundation, PricewaterhouseCoopers, and Tattersall's. The PRACTICAL consortium acknowledges the Intramural Program of the National Human Genome Research Institute for their support.
Funding Information:
A.P. has received funding for travel or speaker's honoraria from the International Parkinson and Movement Disorder Society, International Association of Parkinsonism and Related Disorders, and Swedish Movement Disorder Society; serves as Associate Editor for ; and has received research support from the Swedish government through funding for clinical research within the Swedish National Health Services (ALF), Region Skåne, Swedish Parkinson Foundation (Parkinsonfonden), Skåne University Hospital research grants, and Swedish Parkinson Academy (all in Sweden). Parkinsonism and Related Disorders
Funding Information:
Funding for the International Collaborative Oncological Gene‐Environment Study (iCOGS) infrastructure was from the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH‐F2‐2009‐223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, and C8197/A16565), National Institutes of Health (CA128978) and Post‐Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112—the GAME‐ON initiative), Department of Defense (W81XWH‐10‐1‐0341), Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, Breast Cancer Research Foundation, and Ovarian Cancer Research Fund.
Funding Information:
Genotyping of the OncoArray was supported by the National Institutes of Health (NIH) (U19 CA 148537 for ELucidating Loci Involved in Prostate cancer SuscEptibility [ELLIPSE] project and X01HG007492 to the Center for Inherited Disease Research [CIDR] under contract number HHSN268201200008I) and by Cancer Research UK grant A8197/A16565. Additional analytic support was provided by NIH National Cancer Institute (NCI) U01 CA188392 (PI: Schumacher). The International Lung Cancer Consortium (ILCCO) GWAS was supported by the NIH (U19 CA203654 [INTEGRAL]).
Funding Information:
This research and work received support from Region Skåne, ALF, Swedish Parkinson Foundation, Swedish Parkinson Academy, MultiPark, a strategic research environment at Lund University (all in Sweden).
Funding Information:
The BPC3 was supported by the National Institutes of Health, National Cancer Institute (cooperative agreements U01‐CA98233 to D.J.H., U01‐CA98710 to S.M.G., U01‐CA98216 to E.R., and U01‐CA98758 to B.E.H.; and Intramural Research Program of NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics).
Funding Information:
CAPS GWAS was supported by the Swedish Cancer Foundation (grants 09‐0677, 11‐484, and 12‐823), the Cancer Risk Prediction Center (CRisP; www.crispcenter.org ), a Linneus Centre (contract ID 70867902) financed by the Swedish Research Council, and the Swedish Research Council (grant K2010‐70X‐20,430‐04‐3, 2014‐2269).
Publisher Copyright:
© 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.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
KW - cancer
KW - genetic correlation
KW - Parkinson's disease
KW - pleiotropy
KW - polygenic risk score
UR - http://www.scopus.com/inward/record.url?scp=85148340230&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/36788297
U2 - 10.1002/mds.29337
DO - 10.1002/mds.29337
M3 - Article
C2 - 36788297
AN - SCOPUS:85148340230
SN - 0885-3185
VL - 38
SP - 604
EP - 615
JO - Movement Disorders
JF - Movement Disorders
IS - 4
ER -