Abstract
Psoriasis is a prevalent inflammatory skin disorder, often associated with an increased risk of atherosclerosis. Despite growing evidence suggesting a potential link between psoriasis and acute myocardial infarction (AMI), the causal relationship remains uncertain and is still a subject of debate. This study aims to fill this knowledge gap by utilizing Mendelian randomization (MR) and mediation analysis to systematically evaluate the causal association between psoriasis and AMI. Additionally, we seek to identify potential mediators that may influence this relationship, thereby providing new insights into the underlying mechanisms that could explain the observed association. The psoriasis GWAS dataset (2802 cases, 212,242 controls) was obtained from the FinnGen study, while genetic associations with endothelial selective adhesion molecule (ESAM) and interleukin (IL)-16 levels were derived from meta-analyses by Sun et al (3301 individuals) and Ahola-Olli et al (3483 individuals), respectively. AMI outcome data (3927 cases, 333,272 controls) were extracted from the UK Biobank. Two-sample MR analyses were conducted to assess the causal effects of psoriasis, ESAM, and IL-16 on AMI risk. MR mediation analysis was used to determine whether ESAM and IL-16 mediate the effect of psoriasis on AMI. To minimize the impact of population differences, we employed robust genetic instruments (F > 10) for each exposure, conducted sensitivity analyses (MR-Egger and weighted median) to check for pleiotropy, and ensured the validity of our results across different populations. The genetic liability to psoriasis (odds ratio [OR]: 1.00078; 95% confidence interval [CI]: 1.00008-1.00148; P = .028479), ESAM (OR: 1.00208; 95% CI: 1.00019-1.00397; P = .031089), and IL-16 (OR: 1.00118; 95% CI: 1.00009-1.00227; P = .033826) were associated with higher AMI risks. The proportion of the effects of genetically-predicted psoriasis mediated through genetically-predicted ESMA and IL-16 was 24.8% (95% CI 8.3%-41.2%) and 16.1% (95% CI 5.3%-26.8%), respectively. Genetic liability to psoriasis is correlated with a higher risk of AMI, which is partially mediated by ESAM and IL-16. The targeted intervention of ESAM and IL-16 might help decrease the risk of AMI in psoriasis patients.