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.

Candidate Gene Association Studies in Atopic Dermatitis in Participants of European and Asian Ancestry: A Systematic Review and Meta-Analysis.

Atopic dermatitis (AD) has been extensively investigated for genetic associations utilizing both candidate gene approaches and genome-wide scans. Here, we comprehensively evaluated the available literature to determine the association of candidate genes in AD to gain additional insight into the etiopathogenesis of the disease. We systematically screened all studies that explored the association between polymorphisms and AD risks in cases of European and Asian ancestry and synthesized the available evidence through a random-effects meta-analysis. We identified 99 studies that met our inclusion/exclusion criteria that examined 17 candidate loci in Europeans and 14 candidate genes in Asians. We confirmed the significant associations between FLG variants in both European and Asian populations and AD risk, while synthesis of the available data revealed novel loci mapped to IL18 and TGFB1 genes in Europeans and IL12RB1 and MIF in Asians that have not yet been identified by genome-wide association studies. Our findings provide comprehensive evidence for AD risk loci in cases of both European and Asian ancestries, validating previous associations as well as revealing novel loci that could imply previously unexplored biological pathways.