دورية أكاديمية
Development and Internal Validation of a Clinical and Genetic Risk Score for Rheumatoid Arthritis-Associated Interstitial Lung Disease.
| العنوان: | Development and Internal Validation of a Clinical and Genetic Risk Score for Rheumatoid Arthritis-Associated Interstitial Lung Disease. |
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| المؤلفون: | Wheeler AM; VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA.; University of Nebraska Medical Center, Omaha, NE, USA., Baker JF; University of Pennsylvania & Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA., Riley T; University of Pennsylvania & Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA., Yang Y; University of Nebraska Medical Center, Omaha, NE, USA., Roul P; University of Nebraska Medical Center, Omaha, NE, USA., Wysham KD; VA Puget Sound Health Care System & University of Washington, Seattle, WA, USA., Cannon GW; VA Salt Lake City & University of Utah, Salt Lake City, UT, USA., Kunkel G; VA Salt Lake City & University of Utah, Salt Lake City, UT, USA., Kerr G; Washington D.C. VA, Howard University, & Georgetown University, Washington D.C., USA., Ascherman DP; Pittsburgh VA & University of Pittsburgh, Pittsburgh, PA, USA., Monach P; Boston VA, Boston, MA, USA., Reimold A; Dallas VA & University of Texas Southwestern, Dallas, TX, USA., Poole JA; University of Nebraska Medical Center, Omaha, NE, USA., Merriman TR; University of Alabama at Birmingham, Birmingham, AL, USA., Mikuls TR; VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA.; University of Nebraska Medical Center, Omaha, NE, USA., England BR; VA Nebraska-Western Iowa Health Care System, Omaha, NE, USA.; University of Nebraska Medical Center, Omaha, NE, USA. |
| المصدر: | Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2024 Jan 18. Date of Electronic Publication: 2024 Jan 18. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 100883501 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1462-0332 (Electronic) Linking ISSN: 14620324 NLM ISO Abbreviation: Rheumatology (Oxford) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford, UK : Avenel, N.J. : Oxford University Press ; Distributed by Mercury International, c1999- |
| مستخلص: | Objective: Although clinical and genetic risk factors have been identified for rheumatoid arthritis-associated interstitial lung disease (RA-ILD), there are no current tools allowing for risk stratification. We sought to develop and validate an ILD risk model in a large, multicentre, prospective RA cohort. Methods: Participants in the Veterans Affairs RA (VARA) registry were genotyped for 12 single nucleotide polymorphisms (SNPs) associated with idiopathic pulmonary fibrosis. ILD was validated through systematic record review. A genetic risk score (GRS) was computed from minor alleles weighted by effect size with ILD, using backward selection. The GRS was combined with clinical risk factors within a logistic regression model. Internal validation was completed using bootstrapping, and model performance was assessed by the area under the receiver operating curve (AUC). Results: Of 2,386 participants (89% male, mean age 69.5 years), 9.4% had ILD. Following backward selection, five SNPs contributed to the GRS. The GRS and clinical factors outperformed clinical factors alone in discriminating ILD (AUC 0.675 vs 0.635, p< 0.001). The shrinkage-corrected performance for combined and clinical-only models was 0.667 (95% CI 0.628, 0.712) and 0.623 (95% CI 0.584, 0.651), respectively. Twenty percent of the cohort had a combined risk score below a cut-point with >90% sensitivity. Conclusion: A clinical and genetic risk model discriminated ILD in a large, multicentre RA cohort better than a clinical-only model, excluding 20% of the cohort from low-yield testing. These results demonstrate the potential utility of a GRS in RA-ILD and support further investigation into individualized risk stratification and screening. (Published by Oxford University Press 2024.) |
| فهرسة مساهمة: | Keywords: genetic polymorphism; genetic risk score; interstitial lung disease; rheumatoid arthritis |
| تواريخ الأحداث: | Date Created: 20240120 Latest Revision: 20240120 |
| رمز التحديث: | 20240120 |
| DOI: | 10.1093/rheumatology/keae001 |
| PMID: | 38243706 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1462-0332 |
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| DOI: | 10.1093/rheumatology/keae001 |