Shared genetic risk factors and causal association between psoriasis and coronary artery disease

Abstract

Psoriasis and coronary artery disease (CAD) are related comorbidities that are well established, but whether a genetic basis underlies this is not well studied. We apply trans-disease meta-analysis to 11,024 psoriasis and 60,801 CAD cases, along with their associated controls, identifying one opposing and three shared genetic loci, which are confirmed through colocalization analysis. Combining results from Bayesian credible interval analysis with independent information from genomic, epigenomic, and spatial chromatin organization, we prioritize genes (including IFIH1 and IL23A) that have implications for common molecular mechanisms involved in psoriasis and CAD inflammatory signaling. Chronic systemic inflammation has been associated with CAD and myocardial infarction, and Mendelian randomization analysis finds that CAD as an exposure can have a significant causal effect on psoriasis (OR = 1.11; p = 3×10−6) following adjustment for BMI and waist-hip ratio. Together, these findings suggest that systemic inflammation which causes CAD can increase the risk of psoriasis.

Exploration of the causality of frailty index on psoriasis: A Mendelian randomization study

“…19 A study showed that coronary artery disease increased the risk of psoriasis by MR analysis (OR = 1.11, p = 3E6). 20 Another research indicated that there was a modest causality for psoriasis on type 2 diabetes (p = 1.6E4, OR = 1.01), and a nominally significant causality for type 2 diabetes on psoriasis (p = 0.014, OR = 1.05). 21 Considering that psoriasis was a systemic inflammatory disease, FI seems to be more reasonable and clinically relevant than a single factor to assess psoriasis risk, which has been applied in skin cancer.…”

“…In the GWAS datasets, 49 deficits were used to assess the FI, and many of them were also confirmed to be closely associated with psoriasis, including coronary heart disease, diabetes, rheumatoid disease, periodontal health, cancers and so on 19 . A study showed that coronary artery disease increased the risk of psoriasis by MR analysis (OR = 1.11, p = 3E6) 20 . Another research indicated that there was a modest causality for psoriasis on type 2 diabetes ( p = 1.6E4, OR = 1.01), and a nominally significant causality for type 2 diabetes on psoriasis ( p = 0.014, OR = 1.05) 21 .…”

Causes of Autoimmune Psoriasis and Associated Cardiovascular Disease: Roles of Human Endogenous Retroviruses and Antihypertensive Drugs—A Systematic Review and Meta-analysis

“…A recent Mendelian randomization analysis enriched for non-MHC markers independent of the other risk factors indicates that the chronic systemic inflammation in the coronary artery disease/CAD causes psoriasis (OR=1.11, p =3×10 - 6 ) 10 . This is a weak association, considering the larger sample sizes, and excluded the MHC signals and tissue-driven inflammation.…”

“…Previous studies have largely demonstrated associations between activations of immune cells, the release of inflammation-inducing cytokines, and interleukins from epidermal dendritic/Langerhans cells, and shared genetic risk factors in relation to ERVs, as potential causes for uncontrolled proliferation of dermal keratinocytes in psoriasis and psoriatic CVD [8][9][10] . It remains unclear whether the immune intolerance and induction of inflammation are routed in transcriptional activities of ERV genes partly to suppression of protective genes in keratinocytes and partly to aberrant activation of immune cells are consequences for triggering autoimmune psoriasis.…”

GWAS meta-analysis of psoriasis identifies new susceptibility alleles impacting disease mechanisms and therapeutic targets

“…A series of recent studies have investigated the shared genetic architecture of psoriasis with other disease and health-related traits and have identified putative causal relationships with smoking, obesity and lifetime risk of cardiovascular disease. [37][38][39][40] To further investigate the shared genetic liability and potential causal relationships, we assessed genetic correlation between psoriasis and 345 disease and health-related traits and evaluated asymmetry in the correlation structure (specifically, the mixed fourth moments between effect sizes 41 ) that are consistent with causal relationships.…”