Neuroticism and inflammatory skin diseases: a bidirectional Mendelian randomization study

Previous observational studies have linked inflammatory skin diseases with mental health issues and neuroticism. However, the specific impact of neuroticism and its subclusters (i.e. worry, depressed affect, and sensitivity to environmental stress and adversity) on these conditions remains underexplored. In this work, we explored causal associations between common inflammatory skin diseases and neuroticism. We conducted a two-sample, bidirectional Mendelian randomization (MR) analysis using data from genome-wide association studies in psoriasis, atopic dermatitis, neuroticism and relevant genetic subclusters conducted on participants of European ancestry. Corrections for sample overlap were applied where necessary. We found that psoriasis was causally associated with increased levels of worry (odds ratio, 95% confidence intervals: 1.011, 1.006-1.016, P = 3.84 × 10^-6) while none of the neuroticism subclusters showed significant association with psoriasis. Sensitivity analyses revealed considerable evidence of directional pleiotropy between psoriasis and neuroticism traits. Conversely, genetic liability to atopic dermatitis did not exhibit any significant association with neuroticism traits. Notably, genetically predicted worry was linked to an elevated risk of atopic dermatitis (odds ratio, 95% confidence intervals: 1.227, 1.067-1.41, P = 3.97 × 10^-3). Correction for overlapping samples confirmed the robustness of these results. These findings suggest potential avenues for future interventions aimed at reducing stress and worry among patients with inflammatory skin conditions.