Mendelian Randomization Studies in Psoriasis and Psoriatic Arthritis: A Systematic Review

Jin, Julia; Elhage, Kareem; Spencer, Riley; Davis, Mitchell S.; Hakimi, Marwa; Bhutani, Tina; Liao, Wilson

doi:10.1016/j.jid.2022.11.014

Cited by 11 publications

(4 citation statements)

References 75 publications

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“…Extensive Mendelian randomization approaches have been performed to identify a genetic relationship between psoriasis and several comorbid diseases. A systematic review, in which 27 MR studies were included, was recently published [127]. Exposures like smoking, obesity, cardiovascular disease, and Crohn's disease were identified as causal factors for psoriasis and psoriatic arthritis.…”

Section: Mendelian Randomization In Psoriasismentioning

confidence: 99%

Multi-Omics Approach to Improved Diagnosis and Treatment of Atopic Dermatitis and Psoriasis

Rusiñol,

Puig

2024

IJMS

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Psoriasis and atopic dermatitis fall within the category of cutaneous immune-mediated inflammatory diseases (IMIDs). The prevalence of IMIDs is increasing in industrialized societies, influenced by both environmental changes and a genetic predisposition. However, the exact immune factors driving these chronic, progressive diseases are not fully understood. By using multi-omics techniques in cutaneous IMIDs, it is expected to advance the understanding of skin biology, uncover the underlying mechanisms of skin conditions, and potentially devise precise and personalized approaches to diagnosis and treatment. We provide a narrative review of the current knowledge in genomics, epigenomics, and proteomics of atopic dermatitis and psoriasis. A literature search was performed for articles published until 30 November 2023. Although there is still much to uncover, recent evidence has already provided valuable insights, such as proteomic profiles that permit differentiating psoriasis from mycosis fungoides and β-defensin 2 correlation to PASI and its drop due to secukinumab first injection, among others.

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Section: Mendelian Randomization In Psoriasismentioning

confidence: 99%

Multi-Omics Approach to Improved Diagnosis and Treatment of Atopic Dermatitis and Psoriasis

Rusiñol,

Puig

2024

IJMS

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“…Because alleles are randomly distributed at conception and should be robust to confounding factors and reverse causality, MR can address the limitations of confounding and reverse causation in observational studies from a genetic viewpoint. MR has already been applied to infer causative relationships between various diseases and risk factors [ 25 – 27 ]. Using summary statistics from GWAS, this study employed bidirectional MR analysis to evaluate whether there is a causal relationship between circulating blood cell counts and PE and further explored the role of lymphocyte subgroups in PE.…”

Section: Introductionmentioning

confidence: 99%

Causal association between circulating blood cell traits and pulmonary embolism: a mendelian randomization study

Jiang,

Lin,

Xie

et al. 2024

Thrombosis J

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Background Pulmonary embolism (PE) is a life-threatening thromboembolic disease for which there is limited evidence for effective prevention and treatment. Our goal was to determine whether genetically predicted circulating blood cell traits could influence the incidence of PE. Methods Using single variable Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) analyses, we identified genetic associations between circulating blood cell counts and lymphocyte subsets and PE. GWAS blood cell characterization summary statistics were compiled from the Blood Cell Consortium. The lymphocyte subpopulation counts were extracted from summary GWAS statistics for samples from 3757 individuals that had been analyzed by flow cytometry. GWAS data related to PE were obtained from the FinnGen study. Results According to the SVMR and reverse MR, increased levels of circulating white blood cells (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.81-0.95, p = 0.0079), lymphocytes (OR: 0.90, 95% CI: 0.84-0.97, p = 0.0115), and neutrophils (OR: 0.88, 95% CI: 0.81–0.96, p = 0.0108) were causally associated with PE susceptibility. MVMR analysis revealed that lower circulating lymphocyte counts (OR: 0.84, 95% CI: 0.75-0.94, p = 0.0139) were an independent predictor of PE. According to further MR results, this association may be primarily related to HLA-DR+ natural killer (NK) cells. Conclusions Among European populations, there is a causal association between genetically predicted low circulating lymphocyte counts, particularly low HLA-DR+ NK cells, and an increased risk of PE. This finding supports observational studies that link peripheral blood cells to PE and provides recommendations for predicting and preventing this condition. Graphical Abstract

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“…The incidence of UC has been gradually increasing in recent years. [1][2][3] Psoriasis is an immune-mediated, polygenic hereditary skin disease that can occur in people of any age group, which often recurs and affects approximately 2%-3% of the global population. In recent years, various researchers have studied the correlation between psoriasis and UC, with some differences found in the results obtained.…”

Section: Introductionmentioning

confidence: 99%

“…With unclear pathogenesis and the site of disease mainly involving the rectum, left colon, and even the entire colon, ulcerative colitis (UC) is clinically characterized by symptoms such as diarrhea, abdominal pain, and bloody mucus in the stool, with severe cases leading to complications including intestinal perforation and cancer. The incidence of UC has been gradually increasing in recent years 1–3 . Psoriasis is an immune‐mediated, polygenic hereditary skin disease that can occur in people of any age group, which often recurs and affects approximately 2%–3% of the global population.…”

Section: Introductionmentioning

confidence: 99%

Mendelian randomization analysis of psoriasis and psoriatic arthritis associated with risks of ulcerative colitis

Pan,

Lv,

Wang

et al. 2024

Skin Research and Technology

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ObjectiveThis study is designed to explore the potential causal relationship between psoriasis and psoriatic arthritis (PsA) while investigating the genetic basis shared by these inflammatory diseases.MethodsSignificant single nucleotide polymorphisms (SNPs) associated with UC, psoriasis, and PsA were selected as genetic instrumental variables using Genome‐Wide Association Study (GWAS) datasets. Additionally, Mendelian randomization (MR) methods, including inverse‐variance weighting (IVW), MR‐Egger regression, and Weighted Median (WME), were utilized to evaluate the causal relationships between these diseases. Moreover, sensitivity analysis and heterogeneity testing were conducted to validate the stability of the results.ResultsA total of 123 significant SNPs associated with psoriasis, PsA, and UC were identified as genetic instrumental variables based on GWAS datasets. The analysis revealed a 36% increased risk of UC with psoriasis (odds ratio [OR] = 1.350, 95% confidence interval [CI] = 1.065‐1.729, P = 0.012) and a 32.9% increased risk of UC with PsA (OR = 1.329, 95% CI = 1.176‐1.592, P < 0.001). Further analysis showed a 43.5% increased risk of psoriasis with UC (OR = 1.435, 95% CI = 1.274‐1.831, P < 0.001) and a 45.8% increased risk of PsA with UC (OR = 1.458, 95% CI = 1.166‐1.822, P = 0.0013). In addition, sensitivity analysis and heterogeneity testing demonstrated the high stability of these results. Particularly, neither MR‐Egger regression analysis nor leave‐one‐out analysis revealed significant heterogeneity or pleiotropy bias, indicating the reliability of these causal estimates. Moreover, the use of the MR‐PRESSO further confirmed the positive correlation between psoriasis and UC, and the corrected estimates remained consistent with IVW analysis results after excluding potential outlier SNPs, enhancing the credibility of the analysis.ConclusionsThis study strengthens the understanding of the genetic and causal relationships among UC, psoriasis, and PsA through GWAS and MR methods, revealing the genetic basis they may share. These findings not only provide a novel perspective on the comorbidity mechanisms of these diseases but also offer a valuable reference for the development of future treatment strategies and intervention measures.

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Mendelian Randomization Studies in Psoriasis and Psoriatic Arthritis: A Systematic Review

Cited by 11 publications

References 75 publications

Multi-Omics Approach to Improved Diagnosis and Treatment of Atopic Dermatitis and Psoriasis

Multi-Omics Approach to Improved Diagnosis and Treatment of Atopic Dermatitis and Psoriasis

Causal association between circulating blood cell traits and pulmonary embolism: a mendelian randomization study

Mendelian randomization analysis of psoriasis and psoriatic arthritis associated with risks of ulcerative colitis

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