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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.

SUBMITTER: Patrick MT

PROVIDER: S-EPMC9630428 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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

Patrick Matthew T MT Li Qinmengge Q Wasikowski Rachael R Mehta Nehal N Gudjonsson Johann E JE Elder James T JT Zhou Xiang X Tsoi Lam C LC

Nature communications 20221102 1

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, ...[more]

PMID: 36323703

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Project description:ImportanceInflammation is critical to atherosclerosis. Psoriasis, a chronic inflammatory disease associated with early cardiovascular events and increased aortic vascular inflammation (VI), provides a model to study the process of early atherogenesis. Fludeoxyglucose F 18 positron emission tomography/computed tomography (18F-FDG PET/CT) helps quantify aortic VI, and coronary computed tomography angiography provides coronary artery disease (CAD) assessment through evaluation of total plaque burden (TB) and noncalcified coronary plaque burden (NCB), luminal stenosis, and high-risk plaques (HRP). To our knowledge, association between aortic VI and broad CAD indices has not yet been assessed in a chronic inflammatory disease state. Such a study may provide information regarding the utility of aortic VI in capturing early CAD.ObjectiveTo assess the association between aortic VI and CAD indices, including TB, NCB, luminal stenosis, and HRP prevalence, in psoriasis.Design, setting, and participantsIn a cross-sectional cohort study at the National Institutes of Health, 215 consecutive patients with psoriasis were recruited from surrounding outpatient dermatology practices. All patients underwent 18F-FDG PET/CT for aortic VI assessment, and 190 of 215 patients underwent coronary computed tomography angiography to characterize CAD. The study was conducted between January 1, 2013, and May 31, 2017. Data were analyzed in March 2018.ExposuresAortic VI assessed by 18F-FDG PET/CT.Main outcomes and measuresPrimary outcome: TB and NCB. Secondary outcomes: luminal stenosis and HRP.ResultsAmong 215 patients with psoriasis (mean [SD] age, 50.4 [12.6] years; 126 men [59%]), patients with increased aortic VI had increased TB (standardized β = 0.48; P < .001), and higher prevalence of luminal stenosis (OR, 3.63; 95% CI, 1.71-7.70; P = .001) and HRP (OR, 3.05; 95% CI, 1.42-6.47; P = .004). The aortic VI and TB association was primarily driven by NCB (β = 0.49; P < .001), whereas the aortic VI and HRP association was driven by low-attenuation plaque (OR, 5.63; 95% CI, 1.96-16.19; P = .001). All associations of aortic VI remained significant after adjustment for cardiovascular risk factors: aortic VI and TB (β = 0.23; P < .001), NCB (β = 0.24; P < .001), luminal stenosis (OR, 3.40; 95% CI, 1.40-8.24; P = .007), and HRP (OR, 2.72; 95% CI, 1.08-6.83; P = .03). No association was found between aortic VI and dense-calcified coronary plaque burden.Conclusions and relevanceAortic VI is associated with broad CAD indices, suggesting that aortic VI may be a surrogate for early CAD. Larger prospective studies need to assess these associations longitudinally and examine treatment effects on these outcomes.

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

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

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