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

Abstract

Objectives: To examine associations between 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 randomization (MR) to genome-wide association data (3609 PsA and 7804 psoriasis cases, up to 1.2 million individuals for lifestyle factors and 757 601 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.

Keywords: BMI; PsA; alcohol; education; lifestyle factors; psoriasis; smoking; socioeconomic position.

Fig. 1

Illustration of instrumental variable assumptions and the Wald ratio method The first assumption, relevance, requires that the variant is associated with the exposure. This is the only verifiable assumption. The second assumption, independence, requires the absence of unmeasured confounders of the associations between genetic variants and outcome. Assumption three, exclusion restriction, requires the genetic variants to affect the outcome only through their effect on the exposure of interest. B_GX can be obtained from genome-wide association study (GWAS) of the exposure, and B_GY from GWAS of the outcome. If instrumental variable assumptions are met, then B_GY=B_GX * B_XY, and it follows that the exposure-outcome association can be derived as B_GY/B_GX.

Fig. 2

Cross-sectional associations between psoriatic disease and lifestyle factors and comorbidities Logistic regression models adjusted for age, sex, BMI, education, smoking and alcohol. Lifestyle factors for each psoriatic disease were all entered into a single model (one for smoking status and another for pack years), whereas each comorbidity was examined in a separate adjusted model. CAD: coronary artery disease; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary diease; CWP: chronic widespread pain; GORD: gastro-oesophageal reflux disease; NAFLD: non-alcoholic fatty liver diease; T2DM: type 2 diabetes melitus.

Fig. 3

Mendelian randomization estimates of the effect of lifestyle factors on psoriatic disease and vice versa

Fig. 4

Mendelian randomization estimates of the effect of psoriatic disease on comorbidities and vice versa CAD: coronary artery disease; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary diease; CWP: chronic widespread pain; GORD: gastro-oesophageal reflux disease; IBD: inflammatory bowel disease; NAFLD: non-alcoholic fatty liver diease; T2DM: type 2 diabetes melitus.