Mendelian randomization analysis of the causal relationship between allergic rhinitis and depression and underlying mediation mechanisms.

Background: Epidemiological studies have documented an association between allergic rhinitis (AR) and depression (DE), but causal interpretation is limited by confounding and reverse causation. We applied bidirectional two-sample Mendelian randomization to assess the direction and magnitude of this association and to explore candidate pathways. Methods: Summary-level data were obtained separately from 2 AR GWAS (Study AR1: Results: Across 2 AR instrument sets and 2 depression outcomes, genetic liability to AR was consistently associated with a small increase in depression risk (IVW ORs 1.0105-1.0125), whereas reverse-direction analyses provided no evidence that depression liability increased AR risk. AR liability was nominally associated with sleep duration ( Conclusions: Genetic liability to AR was consistently associated with a small increase in depression risk across 4 dataset pairings. Although the magnitude alone is insufficient to support individual-level clinical decision-making, the concordant findings add etiological evidence for an AR-depression relationship. Sleep duration and anxiety remain plausible but unconfirmed candidate pathways, while the MVMR findings prioritize loneliness for further validation. Total IgE was more consistent with an AR-related biomarker than an independent mediator.