Evaluation of a Genetic Risk Score for Diagnosis of Psoriatic Arthritis

Smith, Mary Patricia; Ly, Karen; Thibodeaux, Quinn; Beck, Kristen M.; Yang, Eric J.; Sanchez, Isabelle M.; Nititham, Joanne; Bhutani, Tina; Liao, Wilson

doi:10.1177/2475530320910814

Cited by 4 publications

(3 citation statements)

References 27 publications

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“…Our prediction models showed only modest ability to discriminate PsA from PsC in the available data sets, which was consistent with the findings of a recently published study by Smith et al (26). For the first approach, we attempted to reproduce a previously published classification pipeline by following the description and published model parameters, which allowed us to reproduce the workflows (13).…”

Section: Discussionsupporting

confidence: 92%

Comparative Genetic Analysis of Psoriatic Arthritis and Psoriasis for the Discovery of Genetic Risk Factors and Risk Prediction Modeling

Soomro

Stadler

Dand

et al. 2022

Arthritis & Rheumatology

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Objectives. Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models.Methods. Genome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)-based heritability estimate (h 2 SNP ) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation.Results. We identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10 −9 ), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10 −45 ) and Wnt signaling (adjusted P = 9.5 × 10 −58 ). The heritability of PsA in this cohort was found to be moderate (h 2 SNP = 0.63), which was similar to the heritability of PsC (h 2 SNP = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data.Conclusion. Key biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of 1535

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Section: Discussionsupporting

confidence: 92%

Comparative Genetic Analysis of Psoriatic Arthritis and Psoriasis for the Discovery of Genetic Risk Factors and Risk Prediction Modeling

Soomro

Stadler

Dand

et al. 2022

Arthritis & Rheumatology

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“…Human Leucocyte Antigen (HLA) was studied in 6 publications ( 19 , 27 – 29 , 35 , 36 ). A family-based study reported an association between PsA and various HLA alleles: HLA-B*27, HLA-B*38, HLA-B*39, and HLA-C*12 ( 27 ).…”

Section: Resultsmentioning

confidence: 99%

Biomarkers in psoriatic arthritis: A meta-analysis and systematic review

et al. 2022

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IntroductionPsoriatic arthritis (PsA) is a chronic inflammatory disease that frequently develops in patients with psoriasis (PsO) but can also occur spontaneously. As a result, PsA diagnosis and treatment is commonly delayed, or even missed outright due to the manifold of clinical presentations that patients often experience. This inevitably results in progressive articular damage to axial and peripheral joints and entheses. As such, patients with PsA frequently experience reduced expectancy and quality of life due to disability. More recently, research has aimed to improve PsA diagnosis and prognosis by identifying novel disease biomarkers.MethodsHere, we conducted a systematic review of the published literature on candidate biomarkers for PsA diagnosis and prognosis in MEDLINE(Pubmed), EMBase and the Cochrane library with the goal to identify clinically applicable PsA biomarkers. Meta-analyses were performed when a diagnostic bone and cartilage turnover biomarker was reported in 2 or moredifferent cohorts of PsA and control. ResultsWe identified 1444 publications and 124 studies met eligibility criteria. We highlighted bone and cartilage turnover biomarkers, genetic markers, and autoantibodies used for diagnostic purposes of PsA, as well as acute phase reactant markers and bone and cartilage turnover biomarkers for activity or prognostic severity purposes. Serum cartilage oligometrix metalloproteinase levels were significantly increased in the PsA sera compared to Healthy Control (HC) with a standardized mean difference (SMD) of 2.305 (95%CI 0.795-3.816, p=0.003) and compared to osteoarthritis (OA) with a SMD of 0.783 (95%CI 0.015-1.551, p=0.046). The pooled serum MMP-3 levels were significantly higher in PsA patients than in PsO patients with a SMD of 0.419 (95%CI 0.119-0.719; p=0.006), but no significant difference was highlighted when PsA were compared to HC. While we did not identify any new genetic biomarkers that would be useful in the diagnosis of PsA, recent data with autoantibodies appear to be promising in diagnosis, but no replication studies have been published. ConclusionIn summary, no specific diagnostic biomarkers for PsA were identified and further studies are needed to assess the performance of potential biomarkers that can distinguish PsA from OA and other chronic inflammatory diseases.

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“…After applying the eligibility criteria of this systematic review to the full texts of the 14 studies, only five studies were included in the review [6,[9][10][11][12]. The reasons for the exclusion of the eight studies are listed in Table 1 [4, [13][14][15][16][17][18][19][20].…”

Section: Results Of Searchmentioning

confidence: 99%

Diagnostic Test Accuracy of Genetic Tests in Diagnosing Psoriasis: A Systematic Review

Mirghani¹,

Alharfy²,

Alanazi³

et al. 2022

Cureus

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The pathogenesis of psoriasis involves the interaction of several environmental and genetic factors. Predicting the disease risk cannot depend on individual genetic alleles. Consequently, some studies have evaluated the use of genetic risk scores that combine several psoriasis susceptibility loci to increase the accuracy of predicting/diagnosing the disease. This meta-analysis summarizes the evidence regarding using genetic risk scores (GRS) in the diagnosis or prediction of psoriasis. A search of MEDLINE/PubMed, the Latin American Caribbean Health Sciences Literature (LILACS) database, Cochrane Library, Scopus, Web of Science, and ProQuest was conducted in July 2022. The primary objective was to record the area under the curve (AUC) for GRS of psoriasis. Secondary objectives included characteristics of studies and patients. The risk of bias (ROB) was assessed using the PROBAST tool. Five studies fulfilled the eligibility criteria of this review. None of the studies described the clinical criteria (reference standard) that were employed to diagnose psoriasis. The AUCs of the 11 GRS models ranged from 0.6029-0.8583 (median: 0.75). Marked heterogeneity was detected (Cochran Q: 1250.051, p < 0.001, and I 2 index: 99.2%). So, pooling of the results of the included studies was not performed. The ROB was high for all studies and clinical application was not described. Genetic risk scores are promising tools for the prediction of psoriasis with fair to good accuracy. However, further research is required to identify the most accurate combination of loci and to validate the scores in variable ethnicities.

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Evaluation of a Genetic Risk Score for Diagnosis of Psoriatic Arthritis

Cited by 4 publications

References 27 publications

Comparative Genetic Analysis of Psoriatic Arthritis and Psoriasis for the Discovery of Genetic Risk Factors and Risk Prediction Modeling

Comparative Genetic Analysis of Psoriatic Arthritis and Psoriasis for the Discovery of Genetic Risk Factors and Risk Prediction Modeling

Biomarkers in psoriatic arthritis: A meta-analysis and systematic review

Diagnostic Test Accuracy of Genetic Tests in Diagnosing Psoriasis: A Systematic Review

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