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. 2025 Aug 12;25(1):786.
doi: 10.1186/s12888-025-07245-w.

Association between depression and asthma: insight from observational and genetic evidence

Tanao Ji  1 , Yue Lv  2 , Jianan Yang  3 , Xianping Diao  3 , Jun Gu  4
Affiliations

Association between depression and asthma: insight from observational and genetic evidence

Tanao Ji et al. BMC Psychiatry. .

Abstract

Background: Depression and asthma share several pathophysiologic risk factors, and their precise connection remains unclear. Our research seeks to assess the relationship between depression and asthma.

Methods: The association between depression and asthma was assessed through a multivariable logistic regression analysis, with data sourced from The National Health and Nutrition Examination Survey (NHANES) 2007-2018 and the English Longitudinal Study of Ageing (ELSA) 2004-2019. Subsequently, a linkage disequilibrium score regression (LDSC) analysis was conducted to evaluate the genetic correlation between depression and asthma. Moreover, a two-sample Mendelian randomization (MR) analysis was conducted by employing genome-wide association study (GWAS) summary statistics by means of both univariable MR (UVMR) and multivariable MR (MVMR).

Results: This study included 31,434 participants from NHANES and 17,021 participants from ELSA for observational research. In the unadjusted model, participants with depression had a significantly increased risk of asthma in comparison to participants without depression, both in NHANES (OR = 2.002, 95%CI: 1.827-2.193, P < 0.001) and in ELSA (OR = 1.753, 95%CI: 1.581-1.943, P < 0.001). After adjusting potential confounders, the results remain significant. The LDSC result revealed a significant positive genetic correlation between depression and asthma (rg = 0.352, P < 0.001).The UVMR results further substantiated a genetically predicted causality of depression on asthma (OR = 1.291, 95%CI: 1.157-1.442, P < 0.001), while the reverse causality does not stand. Similar findings from MVMR were obtained for the causality investigation after adjusting smoking (OR = 1.326, 95%CI: 1.156-1.520, P < 0.001), drinking (OR = 1.375, 95%CI: 1.186-1.593, P < 0.001), and education (OR = 1.425, 95%CI: 1.253-1.621, P < 0.001).

Conclusion: Our findings indicate that depression may play a contributory role in the development of asthma, underscoring the potential benefit of implementing prevention strategies aimed at managing depression to mitigate asthma risk.

Keywords: Asthma; Causal relationship; Depression; Mendelian Randomization; Observational study.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The NHANES protocol has received approval from the NCHS Ethics Review Committee. The ELSA study was approved by the London Multicenter Research Ethics Committee (MREC/01/2/91). All participants provided informed consent. The GWAS data was publicly available and ethics approval and informed consent were not required. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Overview of study design. NHANES, National Health and Nutrition Examination Survey; ELSA, English Longitudinal Study of Ageing; PHQ-9, Patient Health Questionnaire-9; CES-D, Center for Epidemiologic Studies Depression Scale; LDSC, linkage disequilibrium score regression; MR, Mendelian Randomization; SNP, single nucleotide polymorphism; IV, instrumental variable
Fig. 2
Fig. 2
A Subgroup analyses of the association between depression and asthma in NHANES. NHANES National Health and Nutrition Examination Survey, OR odd ratio, CI confidence intervals. B Subgroup analyses of the association between depression and asthma in ELSA. ELSA English Longitudinal Study of Ageing, OR odd ratio, CI confidence intervals
Fig. 3
Fig. 3
Genetically predicted causal effects between depression and asthma. IVW inverse variance weighted, cML-MA constrained maximum likelihood and model averaging, CAUSE causal analysis using summary effect estimates, OR odd ratio, CI confidence intervals
Fig. 4
Fig. 4
Genetically predicted causal effects depression on the risk of asthma using multivariable Mendelian Randomization analysis. OR, odd ratio; CI, confidence intervals
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