Association between psoriatic disease and lifestyle factors and comorbidities: cross-sectional analysis and Mendelian randomisation

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.