OBJECTIVE: Asthma is a common respiratory disease that is believed to be associated with mental disorders. This study aims to assess the correlation and causal relationship between asthma and depression by combining observational and Mendelian randomization (MR) approaches. METHODS: We collected relevant data from the National Health and Nutrition Examination Survey (NHANES) and employed multivariable logistic regression to evaluate the correlation between asthma and depression. Additionally, a two-sample MR analysis was conducted using inverse variance-weighted (IVW) method, along with multiple sensitivity analyses. RESULTS: The observational study included a total of 23 648 participants, and the results showed that asthma patients had an increased risk of developing depression compared to non-asthma individuals (OR 1.26
95% CI 1.04-1.57
P <
0.01). The IVW-MR results from two datasets indicated a potential causal relationship between asthma and depression (EBI dataset: OR 1.141
95% CI 1.051-1.239
P = 0.01
UKB dataset: OR 1.009
95% CI 1.005-1.013
P <
0.01). These findings suggest that asthma may be a risk factor for the onset of depression, increasing the risk of developing depression. CONCLUSION: There is a significant correlation and potential causal relationship between asthma and depression, with asthma being a risk factor for the onset of depression. These findings warrant further research for validation and exploration of preventive and therapeutic measures for depression in asthma patients. Key messages What is already known on this topic-There are some potential associations between asthma and depression based on observational studies, but the results of observational studies are often biased. This study aims to further explore the relationship between asthma and depression through a combination of observational studies and Mendelian randomization (MR) analysis. What this study adds-The observational study results from the National Health and Nutrition Examination Survey database and MR analysis are consistent, indicating that after adjusting for multiple covariates and confounding factors, asthma increases the risk of depression and is a risk factor for depression, with similar results obtained at the genetic level. How this study might affect research, practice or policy-Asthma patients not only need active medication treatment, but also need timely psychological attention, and psychological treatment is more important to a certain extent.