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NSAID medication mediates the causal effect of genetically predicted major depressive disorder on falls: Evidence
1Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Background:
Increasing evidence supports that depression including major depressive disorder (MDD) is associated with an increased risk of falls. However, some studies suggest no association between MDD and falls. Therefore, the specific causal relationship whereby MDD affects the risk of falls remains elusive, and the potential mediators are unclear.
Methods:
Summary-level data for MDD and falls were collected from the Genome-wide association studies (GWAS) in this study. Mendelian randomization (MR) and multivariable MR (MVMR) analyses were performed to evaluate the causal associations between MDD and falls. A Two-step MR analysis was employed to analyze the mediating effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the causal association between MDD and the risk of falls.
Results:
Using the inverse-variance weighted (IVW) method, genetically predicted MDD was associated with an increased risk of falls (β = 0.15, SE = 0.034; P = 1.61E-5). MVMR and two-step MR analyses demonstrated that MDD was a causal determinant of increased falls independent of body mass index (BMI), smoking initiation, and alcohol consumption and that this causal relationship was mediated by NSAID medication.
Limitations:
Extracted GWAS summary statistics are from European ancestry. Stratified analyses by sex and age were not included in our study. Therefore, it is unclear whether the results are the same for other ethnic groups, genders, and ages.
Conclusions:
Our results demonstrate that MDD is independently associated with an increased risk of falls, in which NSAIDs mediate the association. This study suggests that avoiding the use of NSAIDs may reduce the risk of falls in patients diagnosed with MDD.
Insights
Major depressive disorder (MDD) increases fall risk, with nonsteroidal anti-inflammatory drugs (NSAIDs) mediating this effect. Avoiding NSAIDs may help reduce falls in MDD patients.
Area of Science:
- Epidemiology
- Psychiatry
- Pharmacology
Background:
- Major depressive disorder (MDD) is increasingly linked to a higher risk of falls.
- However, the causal relationship and mediating factors between MDD and falls remain unclear.
- Some studies show no association, necessitating further investigation.
Purpose of the Study:
- To investigate the causal relationship between MDD and the risk of falls.
- To identify potential mediators in the association between MDD and falls.
- To explore the mediating role of nonsteroidal anti-inflammatory drugs (NSAIDs) in this relationship.
Main Methods:
- Utilized summary-level data from Genome-wide association studies (GWAS).
- Employed Mendelian randomization (MR) and multivariable MR (MVMR) analyses.
- Conducted a two-step MR analysis to assess NSAID mediation.
Main Results:
- Genetically predicted MDD showed a significant association with an increased risk of falls (P = 1.61E-5).
- MDD causally determined increased falls, independent of BMI, smoking, and alcohol consumption.
- Nonsteroidal anti-inflammatory drug (NSAID) medication was identified as a key mediator.
Conclusions:
- MDD is independently associated with an elevated risk of falls.
- NSAIDs mediate the relationship between MDD and falls.
- Avoiding NSAIDs may potentially decrease fall risk in individuals with MDD.
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