Br J Dermatol. 2023 Oct 24:ljad410. doi: 10.1093/bjd/ljad410. Online ahead of print.
ABSTRACT
BACKGROUND: Co-existing long-term conditions (LTC) in psoriasis and their potential causal associations with the disease are not well-established.
OBJECTIVES: This study aims to determine distinct clusters of LTC in people with psoriasis and the potential bi-directional causal association between these LTC and psoriasis.
METHODS: Using latent class analysis, cross-sectional data of people with psoriasis from the UK Biobank were analysed to identify distinct psoriasis-related co-morbidity profiles. Linkage disequilibrium score regression (LDSR) was applied to compute the genetic correlation between psoriasis and LTC. Two-sample bidirectional Mendelian randomisation (MR) analysis assessed potential causal direction using independent genetic variants that reached genome-wide significance (P < 5 × 10-8).
RESULTS: Five co-morbidity clusters were identified in a population of 10,873 people with psoriasis. LDSR revealed that psoriasis was positively genetically correlated with heart failure (rg = 0.23, p = 8.8 × 10-8), depression (rg = 0.12, p = 2.7 × 10-5), coronary artery disease (CAD) (rg = 0.15, p = 2 × 10-4), and type 2 diabetes (rg = 0.19, p = 3 × 10-3). Genetic liability to CAD was associated with an increased risk of psoriasis (ORIVW = 1.159; 95%CI 1.055-1.274; p = 2 × 10-3). The MR-PRESSO (ORMR-PRESSO = 1.13; 95%CI 1.042-1.228; p = 6 × 10-3) and the MR-RAPS (ORMR-RAPS = 1.149; 95%CI 1.062-1.242; p = 5 × 10-4) approaches corroborate the IVW findings. The weighted median generated similar and consistent effect estimates but was not statistically significant (ORWM = 1.076; 95%CI 0.949-1.221; p = 0.251). Evidence for a suggestive increased risk was detected for CAD (ORIVW = 1.031; 95%CI 1.003-1.059; p = 0.032) and heart failure (ORIVW = 1.019; 95%CI 1.005-1.033; p = 9 × 10-3) in those with genetic liability to psoriasis; however, MR sensitivity analyses did not reach statistical significance.
CONCLUSIONS: Five distinct clusters of psoriasis co-morbidities were observed with these findings to offer opportunities for an integrated approach to comorbidity prevention and treatment. Co-existing LTC share with psoriasis common genetic and non-genetic risk factors, and aggressive lifestyle modification in these people is anticipated to have an impact beyond psoriasis risk. Genetically predicted coronary artery disease is possibly associated with an increased risk of psoriasis, altering our prior knowledge.
PMID:37874776 | DOI:10.1093/bjd/ljad410
