Dataset Information

Systematic Screening of Associations between Medication Use and Risk of Neurodegenerative Diseases Using a Mendelian Randomization Approach.

ABSTRACT:

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, p = 0.031), thyroid preparations (OR = 0.948, 95% CI = 0.909-0.988, p = 0.011), and immunosuppressants (OR = 0.879, 95% CI = 0.789-0.979, p = 0.018) was associated with a decreased risk of AD. Genetic proxies for thyroid preparations (OR = 0.934, 95% CI = 0.884-0.988, p = 0.017), immunosuppressants (OR = 0.825, 95% CI = 0.699-0.973, p = 0.022), and glucocorticoids (OR = 0.862, 95% CI = 0.756-0.983, p = 0.027) were causally associated with a decreased risk of PD. Genetically determined antithrombotic agents (OR = 1.234, 95% CI = 1.042-1.461, p = 0.015), HMG CoA reductase inhibitors (OR = 1.085, 95% CI = 1.025-1.148, p = 0.005), and salicylic acid and derivatives (OR = 1.294, 95% CI = 1.078-1.553, p = 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.

SUBMITTER: Wang W

PROVIDER: S-EPMC10377701 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Systematic Screening of Associations between Medication Use and Risk of Neurodegenerative Diseases Using a Mendelian Randomization Approach.

Wang Wenjing W Zhang Linjing L Cao Wen W Xia Kailin K Huo Junyan J Huang Tao T Fan Dongsheng D

Biomedicines 20230707 7

<h4>Background</h4>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).<h4>Methods</h4>A two-sample mendelian randomization (MR) approach was ...[more]

PMID: 37509570

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Project description:Rationale & objectiveThe association between cannabis use and chronic kidney disease (CKD) is controversial. We aimed to assess association of CKD with cannabis use in a large cohort study and then assess causality using Mendelian randomization with a genome-wide association study (GWAS).Study designRetrospective cohort study and genome-wide association study.Setting & participantsThe retrospective study was conducted on the All of Us cohort (N=223,354). Genetic instruments for cannabis use disorder were identified from 3 GWAS: the Psychiatric Genomics Consortium Substance Use Disorders, iPSYCH, and deCODE (N=384,032). Association between genetic instruments and CKD was investigated in the CKDGen GWAS (N > 1.2 million).ExposureCannabis consumption.OutcomesCKD outcomes included: cystatin-C and creatinine-based kidney function, proteinuria, and blood urea nitrogen.Analytical approachWe conducted association analyses to test for frequency of cannabis use and CKD. To evaluate causality, we performed a 2-sample Mendelian randomization.ResultsIn the retrospective study, compared to former users, less than monthly (OR, 1.01; 95% CI, 0.87-1.18; P = 0.87) and monthly cannabis users (OR, 1.15; 95% CI, 0.86-1.52; P = 0.33) did not have higher CKD odds. Conversely, weekly (OR, 1.28; 95% CI, 1.01-1.60; P = 0.04) and daily use (OR, 1.25; 95% CI, 1.04-1.50; P = 0.02) was significantly associated with CKD, adjusted for multiple confounders. In Mendelian randomization, genetic liability to cannabis use disorder was not associated with increased odds for CKD (OR, 1.00; 95% CI, 0.99-1.01; P = 0.96). These results were robust across different Mendelian randomization techniques and multiple kidney traits.LimitationsLikely underreporting of cannabis use. In Mendelian randomization, genetic instruments were identified in the GWAS that included individuals primarily of European ancestry.ConclusionsDespite the epidemiological association between cannabis use and CKD, there was no evidence of a causal effect, indicating confounding in observational studies.

Dataset Information

Systematic Screening of Associations between Medication Use and Risk of Neurodegenerative Diseases Using a Mendelian Randomization Approach.

Background

Methods

Results

Conclusions

Publications

Systematic Screening of Associations between Medication Use and Risk of Neurodegenerative Diseases Using a Mendelian Randomization Approach.

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