Bidirectional two-sample mendelian randomization analysis identifies a causal relationship between major depressive disorder and allergic diseases.

Background: Several studies have indicated an association between major depressive disorder (MDD) and allergic diseases (ADs), but the exact causal relationship remains inconclusive. Thus, this study aimed to explore the causal relationship between MDD and ADs employing bidirectional two-sample Mendelian randomization (MR).

Method: The summary statistics for MDD were sourced from the Psychiatric Genomics Consortium. Single nucleotide polymorphisms (SNPs) associated with allergic asthma (AAS), allergic rhinitis (AR), and atopic dermatitis, were extracted from the FinnGen Consortium. The inverse variance weighted was primarily used in this MR analysis, with other methods as supplements. Several sensitivity analyses were performed to evaluate heterogeneity and horizontal pleiotropy. A reverse MR analysis was also conducted.

Results: The inverse variance weighted method demonstrated a nominally significant association between MDD and an increased risk of AR (OR = 1.191, 95% confidence interval [CI] [1.006, 1.411], p = .042); after removing the two outlier Single nucleotide polymorphisms, a causal relationship was found between genetic susceptibility to MDD and AAS (OR = 1.418, 95% CI [1.207, 1.666], p = .000022). These results passed the heterogeneity and horizontal pleiotropy tests. However, MDD did not cause atopic dermatitis according to our results (OR = 1.049, 95% CI [0.903, 1.219], p = .53). Furthermore, reverse MR analysis unsupported ADs cause MDD.

Conclusion: This MR study suggested a nominally significant causal relationship between MDD and increased risk of AR, and a specific condition-based causal relationship between MDD and AAS. In the future, these results need to be validated further. (PsycInfo Database Record (c) 2025 APA, all rights reserved).