Development and Internal Validation of a Clinical and Genetic Risk Score for Rheumatoid Arthritis-Associated Interstitial Lung Disease

Details

• Personal Author:
  Ascherman DP ; Baker JF ; Cannon GW ; England BR ; Kerr G ; Kunkel G ; Merriman TR ; Mikuls TR ; Monach P ; Poole JA ; Reimold A ; Riley T ; Roul P ; Wheeler AM ; Wysham KD ; Yang Y
• Description:
  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 2386 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. [Description provided by NIOSH]
• Subjects:
  Cohort Studies Fibrosis Genetics Lung Diseases Occupational Health Respiratory Tract Diseases Risk Assessment Safety
• Keywords:
  Author Keywords: Genetic Polymorphism Cohort Studies Genetic Risk Score Interstitial Lung Disease Lung Disease Rheumatoid Arthritis Rheumatoid Disorders Risk Analysis
• ISSN:
  1462-0324
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Alabama ; Birmingham Region [OSHA] ; Boston Region [OSHA] ; Dallas Region [OSHA] ; Denver Region [OSHA] ; District of Columbia ; Kansas City Region [OSHA] ; Massachusetts ; Nebraska ; Pennsylvania ; Philadelphia Region [OSHA] ; San Francisco Region [OSHA] ; Texas ; Utah ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  268-275
• Volume:
  64
• Issue:
  1
• NIOSHTIC Number:
  nn:20070440
• Citation:
  Rheumatology 2025 Jan; 64(1):268-275
• Contact Point Address:
  Bryant R. England, Division of Rheumatology & Immunology, Department of Internal Medicine, 986270 Nebraska Medical Center, Omaha, NE 68198-6270
• Email:
  bryant.england@unmc.edu
• Federal Fiscal Year:
  2025
• Performing Organization:
  University of Nebraska Medical Center
• Peer Reviewed:
  True
• Start Date:
  20210901
• Source Full Name:
  Rheumatology
• End Date:
  20250831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e6d4f98f1fa156de5ae9871dd3c1cb6266c4f348031bb34878ea650341a99554d4ac4af155986bd141a724e3f36933834059754edbd41d3d9b57ce52a37ef453
• Download URL:
  https://stacks.cdc.gov/view/cdc/208648/cdc_208648_DS1.pdf
• File Type:
  [PDF - 467.04 KB ]