Systematic Screening of Associations between Medication Use and Risk of Neurodegenerative Diseases Using a Mendelian Randomization Approach
Background: Systematically assessing the causal associations between medications and neurodegenerative diseases is significant in identifying disease etiology and novel therapies. Here, we investigated the putative causal associations between 23 existing medication categories and major neurodegenera...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/7/1930 |
| _version_ | 1827733751234297856 |
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| author | Wenjing Wang Linjing Zhang Wen Cao Kailin Xia Junyan Huo Tao Huang Dongsheng Fan |
| author_facet | Wenjing Wang Linjing Zhang Wen Cao Kailin Xia Junyan Huo Tao Huang Dongsheng Fan |
| author_sort | Wenjing Wang |
| collection | DOAJ |
| description | Background: Systematically assessing the causal associations between medications and neurodegenerative diseases is significant in identifying disease etiology and novel therapies. Here, we investigated the putative causal associations between 23 existing medication categories and major neurodegenerative diseases (NDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Methods: A two-sample mendelian randomization (MR) approach was conducted. Estimates were calculated using the inverse-variance weighted (IVW) method as the main model. A sensitivity analysis and a pleiotropy analysis were performed to identify potential violations. Results: Genetically predisposition to antihypertensives (OR = 0.809, 95% CI = 0.668–0.981, <i>p</i> = 0.031), thyroid preparations (OR = 0.948, 95% CI = 0.909–0.988, <i>p</i> = 0.011), and immunosuppressants (OR = 0.879, 95% CI = 0.789–0.979, <i>p</i> = 0.018) was associated with a decreased risk of AD. Genetic proxies for thyroid preparations (OR = 0.934, 95% CI = 0.884–0.988, <i>p</i> = 0.017), immunosuppressants (OR = 0.825, 95% CI = 0.699–0.973, <i>p</i> = 0.022), and glucocorticoids (OR = 0.862, 95% CI = 0.756–0.983, <i>p</i> = 0.027) were causally associated with a decreased risk of PD. Genetically determined antithrombotic agents (OR = 1.234, 95% CI = 1.042–1.461, <i>p</i> = 0.015), HMG CoA reductase inhibitors (OR = 1.085, 95% CI = 1.025–1.148, <i>p</i> = 0.005), and salicylic acid and derivatives (OR = 1.294, 95% CI = 1.078–1.553, <i>p</i> = 0.006) were associated with an increased risk of ALS. Conclusions: We presented a systematic view concerning the causal associations between medications and NDs, which will promote the etiology discovery, drug repositioning and patient management for NDs. |
| first_indexed | 2024-03-11T01:16:32Z |
| format | Article |
| id | doaj.art-4781b2e70e09419dbe4150c68d700e0b |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T01:16:32Z |
| publishDate | 2023-07-01 |
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| spelling | doaj.art-4781b2e70e09419dbe4150c68d700e0b2023-11-18T18:27:02ZengMDPI AGBiomedicines2227-90592023-07-01117193010.3390/biomedicines11071930Systematic Screening of Associations between Medication Use and Risk of Neurodegenerative Diseases Using a Mendelian Randomization ApproachWenjing Wang0Linjing Zhang1Wen Cao2Kailin Xia3Junyan Huo4Tao Huang5Dongsheng Fan6Department of Neurology, Peking University Third Hospital, Beijing 100191, ChinaDepartment of Neurology, Peking University Third Hospital, Beijing 100191, ChinaDepartment of Neurology, Peking University Third Hospital, Beijing 100191, ChinaDepartment of Neurology, Peking University Third Hospital, Beijing 100191, ChinaDepartment of Neurology, Peking University Third Hospital, Beijing 100191, ChinaDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, ChinaDepartment of Neurology, Peking University Third Hospital, Beijing 100191, ChinaBackground: Systematically assessing the causal associations between medications and neurodegenerative diseases is significant in identifying disease etiology and novel therapies. Here, we investigated the putative causal associations between 23 existing medication categories and major neurodegenerative diseases (NDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Methods: A two-sample mendelian randomization (MR) approach was conducted. Estimates were calculated using the inverse-variance weighted (IVW) method as the main model. A sensitivity analysis and a pleiotropy analysis were performed to identify potential violations. Results: Genetically predisposition to antihypertensives (OR = 0.809, 95% CI = 0.668–0.981, <i>p</i> = 0.031), thyroid preparations (OR = 0.948, 95% CI = 0.909–0.988, <i>p</i> = 0.011), and immunosuppressants (OR = 0.879, 95% CI = 0.789–0.979, <i>p</i> = 0.018) was associated with a decreased risk of AD. Genetic proxies for thyroid preparations (OR = 0.934, 95% CI = 0.884–0.988, <i>p</i> = 0.017), immunosuppressants (OR = 0.825, 95% CI = 0.699–0.973, <i>p</i> = 0.022), and glucocorticoids (OR = 0.862, 95% CI = 0.756–0.983, <i>p</i> = 0.027) were causally associated with a decreased risk of PD. Genetically determined antithrombotic agents (OR = 1.234, 95% CI = 1.042–1.461, <i>p</i> = 0.015), HMG CoA reductase inhibitors (OR = 1.085, 95% CI = 1.025–1.148, <i>p</i> = 0.005), and salicylic acid and derivatives (OR = 1.294, 95% CI = 1.078–1.553, <i>p</i> = 0.006) were associated with an increased risk of ALS. Conclusions: We presented a systematic view concerning the causal associations between medications and NDs, which will promote the etiology discovery, drug repositioning and patient management for NDs.https://www.mdpi.com/2227-9059/11/7/1930neurodegenerative diseasesAlzheimer’s disease (AD)Parkinson’s disease (PD)amyotrophic lateral sclerosis (ALS)medication use |
| spellingShingle | Wenjing Wang Linjing Zhang Wen Cao Kailin Xia Junyan Huo Tao Huang Dongsheng Fan Systematic Screening of Associations between Medication Use and Risk of Neurodegenerative Diseases Using a Mendelian Randomization Approach Biomedicines neurodegenerative diseases Alzheimer’s disease (AD) Parkinson’s disease (PD) amyotrophic lateral sclerosis (ALS) medication use |
| title | Systematic Screening of Associations between Medication Use and Risk of Neurodegenerative Diseases Using a Mendelian Randomization Approach |
| title_full | Systematic Screening of Associations between Medication Use and Risk of Neurodegenerative Diseases Using a Mendelian Randomization Approach |
| title_fullStr | Systematic Screening of Associations between Medication Use and Risk of Neurodegenerative Diseases Using a Mendelian Randomization Approach |
| title_full_unstemmed | Systematic Screening of Associations between Medication Use and Risk of Neurodegenerative Diseases Using a Mendelian Randomization Approach |
| title_short | Systematic Screening of Associations between Medication Use and Risk of Neurodegenerative Diseases Using a Mendelian Randomization Approach |
| title_sort | systematic screening of associations between medication use and risk of neurodegenerative diseases using a mendelian randomization approach |
| topic | neurodegenerative diseases Alzheimer’s disease (AD) Parkinson’s disease (PD) amyotrophic lateral sclerosis (ALS) medication use |
| url | https://www.mdpi.com/2227-9059/11/7/1930 |
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