Language

English

Publication Date

4-1-2026

Journal

Seminars in Arthritis and Rheumatism

DOI

10.1016/j.semarthrit.2026.152937

PMID

41713227

PMCID

PMC13389969

PubMedCentral® Posted Date

7-23-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Objective: We aimed to identify the strongest individual gene-respiratory interactions for rheumatoid arthritis (RA) risk.

Methods: This case-control study used the Mayo Clinic (MC) and Mass General Brigham (MGB) biobanks for discovery and validation, respectively. We matched criteria-confirmed incident RA cases to four non-RA controls on age, sex, and duration electronic health record (EHR) history. Genetic exposures included known RA risk alleles. We identified respiratory diseases by codes and defined "respiratory burden" as the total number of respiratory codes divided by EHR duration before index date of RA. Using logistic regression models adjusting for potential confounders, we estimated odds ratios (OR) with 95% confidence intervals (CI) for the interactions between genetic and respiratory exposures for RA risk.

Results: We identified 1,125 incident RA cases and 4,495 non-RA controls (mean age 64 years, 70% female in MC; 54 years, 76% female in MGB). In MC, both interstitial lung disease (OR 1.55, 95% CI 1.00-2.40) and overall respiratory burden (OR 1.67, 95% CI 1.30-2.15) were associated with incident RA. Four novel gene-respiratory interactions validated in MGB including CD83/RNF182 (rs12530098)-acute pharyngitis for seronegative RA (OR 4.06 [95% CI 1.61-10.3] MC; 3.68 [95% CI 1.42-9.56] MGB) and JARID2 (rs113532504)-asthma for seropositive RA (OR 2.66 [95% CI 1.30-5.44] MC; 1.93 [95% CI 1.20-3.08] MGB). The CD83/RNF182-acute pharyngitis interaction exhibited the strongest dose-response association (OR 8.54 [95% CI 1.59-45.9] for highest respiratory burden).

Conclusion: This study identified novel respiratory risk factors and gene-respiratory endotypes for RA, which may be useful for RA prevention, diagnosis, and treatment.

Keywords

Humans, Arthritis, Rheumatoid, Female, Case-Control Studies, Male, Middle Aged, Genetic Predisposition to Disease, Risk Factors, Aged, Respiratory Tract Diseases

Comments

This article has been corrected. See Semin Arthritis Rheum. 2026 Oct 24;81:153086.

Published Open-Access

yes

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