Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers
Sugier, Pierre Emmanuel ; Puschmann, Andreas LU
; Rödström, Emil Ygland
LU
and Sharma, Manu
(2023)
In Movement Disorders
38(4).
p.604-615
- 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,... (More)
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.
(Less)
- author
- Sugier, Pierre Emmanuel
; Puschmann, Andreas
LU
; Rödström, Emil Ygland
LU
and Sharma, Manu
- author collaboration
- organization
- publishing date
- 2023-04
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cancer, genetic correlation, Parkinson's disease, pleiotropy, polygenic risk score
- in
- Movement Disorders
- volume
- 38
- issue
- 4
- pages
- 604 - 615
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:36788297
- scopus:85148340230
- ISSN
- 0885-3185
- DOI
- 10.1002/mds.29337
- language
- English
- LU publication?
- yes
- additional info
- 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.
- id
- 6083553e-0f74-4731-a90b-7c8107e7472c
- date added to LUP
- 2023-08-31 20:50:05
- date last changed
- 2024-04-20 02:22:14
@article{6083553e-0f74-4731-a90b-7c8107e7472c,
abstract = {{<p>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<sub>corr</sub> = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (G<sub>corr</sub> = 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.</p>}},
author = {{Sugier, Pierre Emmanuel and Puschmann, Andreas and Rödström, Emil Ygland and Sharma, Manu}},
issn = {{0885-3185}},
keywords = {{cancer; genetic correlation; Parkinson's disease; pleiotropy; polygenic risk score}},
language = {{eng}},
number = {{4}},
pages = {{604--615}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Movement Disorders}},
title = {{Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers}},
url = {{http://dx.doi.org/10.1002/mds.29337}},
doi = {{10.1002/mds.29337}},
volume = {{38}},
year = {{2023}},
}