Objectives To examine associations between psoriatic arthritis (PsA) and psoriasis vs lifestyle factors and comorbidities by triangulating observational and genetic evidence. Methods We analysed cross-sectional data from the UK Biobank (1836 PsA, 8995 psoriasis, 36 000 controls) to describe the association between psoriatic disease and lifestyle factors (including BMI and smoking) and 15 comorbidities (including diabetes and coronary artery disease (CAD)) using logistic models adjusted for age, sex and lifestyle factors. We applied bidirectional Mendelian randomisation (MR) to genome-wide association data (3609 PsA and 7804 psoriasis cases, up to 1.2 million individuals for lifestyle factors and 757601 for comorbidities) to examine causal direction, using the inverse-variance weighted method. Results BMI was cross-sectionally associated with risk of PsA (OR 1.31 per 5 kg/m2 increase; 95%CI 1.26–1.37) and psoriasis (OR 1.23; 1.20–1.26), with consistent MR estimates (PsA OR 1.38; 1.14–1.67; psoriasis OR 1.36; 1.18–1.58). In both designs, smoking was more strongly associated with psoriasis than PsA. PsA and psoriasis were cross-sectionally associated with diabetes (OR 1.35 and 1.39, respectively) and CAD (OR 1.56 and 1.38, respective). Genetically predicted glycated haemoglobin (surrogate for diabetes) increased PsA risk (OR 1.18 per 6.7 mmol/mol increase; 1.02–1.36) but not psoriasis. Genetic liability to PsA (OR 1.05; 1.003–1.09) and psoriasis (OR 1.03; 1.001–1.06) were associated with increased risk of CAD. Conclusion Observational and genetic evidence converge to suggest that BMI and glycaemic control are associated with increased psoriatic disease risk, while psoriatic disease is associated with increased CAD risk. Further research is needed to understand the mechanism of these associations.

中文翻译：

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银屑病与生活方式因素和合并症之间的关联：横断面分析和孟德尔随机化

目的 通过对观察和遗传证据进行三角测量，检查银屑病关节炎 (PsA) 和银屑病与生活方式因素和合并症之间的关联。方)) 使用针对年龄、性别和生活方式因素进行调整的逻辑模型。我们将双向孟德尔随机化 (MR) 应用于全基因组关联数据（3609 例 PsA 和 7804 例银屑病病例，生活方式因素多达 120 万人，合并症多达 757601 例），使用逆方差加权方法检查因果方向。结果 BMI 与 PsA 风险（每增加 5 kg/m2 OR 1.31；95%CI 1.26–1.37）和银屑病风险（OR 1.23；1.20–1.26）横断面相关，MR 估计值一致（PsA OR 1.38；1.14– 1.67；银屑病或 1.36；1.18–1.58）。在这两种设计中，与 PsA 相比，吸烟与银屑病的相关性更强。PsA 和银屑病与糖尿病（分别为 OR 1.35 和 1.39）和 CAD（分别为 OR 1.56 和 1.38）横断面相关。遗传预测的糖化血红蛋白（糖尿病的替代物）会增加 PsA 风险（每 6.7 mmol/mol 增加 OR 1.18；1.02–1.36），但不会增加银屑病风险。PsA (OR 1.05; 1.003–1.09) 和银屑病 (OR 1.03; 1.001–1.06) 的遗传易感性与 CAD 风险增加相关。结论 观察和遗传证据一致表明 BMI 和血糖控制与银屑病风险增加相关，而银屑病与 CAD 风险增加相关。需要进一步研究以了解这些关联的机制。