ArticleClinical, cosmetic and investigational dermatology2026
Disentangling Nicotine vs Non-Nicotine Components of Tobacco Exposure in Psoriasis and Psoriatic Arthritis: A Multivariable and Trans-Ethnic Mendelian Randomization Study.
Article in Clinical, cosmetic and investigational dermatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: To disentangle tobacco constituents in psoriasis, we contrasted nicotine exposure-proxied by the nicotine metabolite ratio (NMR)-with smoking intensity (cigarettes per day, CPD) and evaluated cross-ancestry effects. Methods: This study applied multivariable Mendelian randomization (MR) jointly modeling genetically proxied NMR (instrumented using variants from a European-ancestry GWAS) and CPD to estimate their independent effects on liability to psoriasis and psoriatic arthritis (PsA). Chronic obstructive pulmonary disease (COPD) served as a positive control. Cross-ancestry generalizability was tested using a trans-ethnic MR (TEMR) framework under conditional likelihood with Nelder-Mead optimization. Sensitivity analyses assessed pleiotropy, heterogeneity, directionality (Steiger), MRLap, RadialMR, and multiple testing (Benjamini-Hochberg). Results: NMR showed an independent association with higher PsA risk irrespective of CPD (OR = 1.104, 95% CI: 1.039-1.174). CPD retained an independent effect on overall psoriasis after conditioning on NMR (OR = 1.305, 95% CI: 1.082-1.573), while the NMR effect on psoriasis attenuated (P > 0.05). In univariable MR, genetically predicted NMR increased psoriasis risk in Europeans (EUR; OR = 1.032, 95% CI: 1.013-1.051). CPD associated with psoriasis in EUR (OR = 1.130, 95% CI: 1.031-1.239) and strongly in Hispanics (HIS; OR = 1.448, 95% CI: 1.434-1.463), with suggestive evidence in East Asians. Reverse-direction MR indicated psoriasis liability correlated with lower CPD across EUR, EAS, AFR, and HIS (β < 0, Conclusion: This study supports ancestry-specific differences and suggests distinct roles of nicotine-related versus non-nicotine tobacco smoke constituents in psoriasis and its subtypes, while the underlying biological mechanisms remain to be clarified.
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