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Protective effect of antihypertensive drugs on the risk of Parkinson’s disease lacks causal evidence from mendelian randomization

Background: Evidence from observational studies concerning the causal role of blood pressure (BP) and antihypertensive medications (AHM) on Parkinson’s disease (PD) remains inconclusive. A two-sample Mendelian randomization (MR) study was performed to evaluate the unconfounded association of genetic...

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Autores principales: Jiang, Zheng, Gu, Xiao-Jing, Su, Wei-Ming, Duan, Qing-Qing, Ren, Yan-Lin, Li, Ju-Rong, Chi, Li-Yi, Wang, Yi, Cao, Bei, Chen, Yong-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9995445/
https://www.ncbi.nlm.nih.gov/pubmed/36909159
http://dx.doi.org/10.3389/fphar.2023.1107248
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author Jiang, Zheng
Gu, Xiao-Jing
Su, Wei-Ming
Duan, Qing-Qing
Ren, Yan-Lin
Li, Ju-Rong
Chi, Li-Yi
Wang, Yi
Cao, Bei
Chen, Yong-Ping
author_facet Jiang, Zheng
Gu, Xiao-Jing
Su, Wei-Ming
Duan, Qing-Qing
Ren, Yan-Lin
Li, Ju-Rong
Chi, Li-Yi
Wang, Yi
Cao, Bei
Chen, Yong-Ping
author_sort Jiang, Zheng
collection PubMed
description Background: Evidence from observational studies concerning the causal role of blood pressure (BP) and antihypertensive medications (AHM) on Parkinson’s disease (PD) remains inconclusive. A two-sample Mendelian randomization (MR) study was performed to evaluate the unconfounded association of genetic proxies for BP and first-line AHMs with PD. Methods: Instrumental variables (IV) from the genome-wide association study (GWAS) for BP traits were used to proxy systolic BP (SBP), diastolic BP, and pulse pressure. SBP-associated variants either located within encoding regions or associated with the expression of AHM targets were selected and then scaled to proxy therapeutic inhibition of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, and thiazides. Positive control analyses on coronary heart disease (CHD) and stroke were conducted to validate the IV selection. Summary data from GWAS for PD risk and PD age at onset (AAO) were used as outcomes. Results: In positive control analyses, genetically determined BP traits and AHMs closely mimicked the observed causal effect on CHD and stroke, confirming the validity of IV selection methodology. In primary analyses, although genetic proxies identified by “encoding region-based method” for β-blockers were suggestively associated with a delayed PD AAO (Beta: 0.115; 95% CI: 0.021, 0.208; p = 1.63E-2; per 10-mmHg lower), sensitivity analyses failed to support this association. Additionally, MR analyses found little evidence that genetically predicted BP traits, overall AHM, or other AHMs affected PD risk or AAO. Conclusion: Our data suggest that BP and commonly prescribed AHMs may not have a prominent role in PD etiology.
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spelling pubmed-99954452023-03-10 Protective effect of antihypertensive drugs on the risk of Parkinson’s disease lacks causal evidence from mendelian randomization Jiang, Zheng Gu, Xiao-Jing Su, Wei-Ming Duan, Qing-Qing Ren, Yan-Lin Li, Ju-Rong Chi, Li-Yi Wang, Yi Cao, Bei Chen, Yong-Ping Front Pharmacol Pharmacology Background: Evidence from observational studies concerning the causal role of blood pressure (BP) and antihypertensive medications (AHM) on Parkinson’s disease (PD) remains inconclusive. A two-sample Mendelian randomization (MR) study was performed to evaluate the unconfounded association of genetic proxies for BP and first-line AHMs with PD. Methods: Instrumental variables (IV) from the genome-wide association study (GWAS) for BP traits were used to proxy systolic BP (SBP), diastolic BP, and pulse pressure. SBP-associated variants either located within encoding regions or associated with the expression of AHM targets were selected and then scaled to proxy therapeutic inhibition of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, and thiazides. Positive control analyses on coronary heart disease (CHD) and stroke were conducted to validate the IV selection. Summary data from GWAS for PD risk and PD age at onset (AAO) were used as outcomes. Results: In positive control analyses, genetically determined BP traits and AHMs closely mimicked the observed causal effect on CHD and stroke, confirming the validity of IV selection methodology. In primary analyses, although genetic proxies identified by “encoding region-based method” for β-blockers were suggestively associated with a delayed PD AAO (Beta: 0.115; 95% CI: 0.021, 0.208; p = 1.63E-2; per 10-mmHg lower), sensitivity analyses failed to support this association. Additionally, MR analyses found little evidence that genetically predicted BP traits, overall AHM, or other AHMs affected PD risk or AAO. Conclusion: Our data suggest that BP and commonly prescribed AHMs may not have a prominent role in PD etiology. Frontiers Media S.A. 2023-02-23 /pmc/articles/PMC9995445/ /pubmed/36909159 http://dx.doi.org/10.3389/fphar.2023.1107248 Text en Copyright © 2023 Jiang, Gu, Su, Duan, Ren, Li, Chi, Wang, Cao and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Jiang, Zheng
Gu, Xiao-Jing
Su, Wei-Ming
Duan, Qing-Qing
Ren, Yan-Lin
Li, Ju-Rong
Chi, Li-Yi
Wang, Yi
Cao, Bei
Chen, Yong-Ping
Protective effect of antihypertensive drugs on the risk of Parkinson’s disease lacks causal evidence from mendelian randomization
title Protective effect of antihypertensive drugs on the risk of Parkinson’s disease lacks causal evidence from mendelian randomization
title_full Protective effect of antihypertensive drugs on the risk of Parkinson’s disease lacks causal evidence from mendelian randomization
title_fullStr Protective effect of antihypertensive drugs on the risk of Parkinson’s disease lacks causal evidence from mendelian randomization
title_full_unstemmed Protective effect of antihypertensive drugs on the risk of Parkinson’s disease lacks causal evidence from mendelian randomization
title_short Protective effect of antihypertensive drugs on the risk of Parkinson’s disease lacks causal evidence from mendelian randomization
title_sort protective effect of antihypertensive drugs on the risk of parkinson’s disease lacks causal evidence from mendelian randomization
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9995445/
https://www.ncbi.nlm.nih.gov/pubmed/36909159
http://dx.doi.org/10.3389/fphar.2023.1107248
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