Journal
ANNALS OF THE RHEUMATIC DISEASES
Volume 80, Issue 12, Pages 1530-1536Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/annrheumdis-2021-220698
Keywords
rheumatoid arthritis; pulmonary fibrosis; polymorphism; genetic
Categories
Funding
- Turku University Hospital Research Foundation
- Sigrid Juselius Foundation
- Horizon 2020 Research and Innovation Programme [667301]
- University of Helsinki HiLIFE Fellow grants 2017-2020
- Academy of Finland Center of Excellence in Complex Disease Genetics [312062, 312074]
- Academy of Finland [331671, 285380, 334229]
- Business Finland [HUS 4685/31/2016, UH 4386/31/2016]
- AbbVie Inc.
- AstraZeneca UK Ltd.
- Biogen MA Inc.
- Celgene Corporation
- Celgene International II Sarl
- Genentech Inc.
- Merck Sharp Dohme Corp.
- Pfizer Inc.
- GlaxoSmithKline Intellectual Property Development Ltd.
- Sanofi US Services Inc.
- Maze Therapeutics Inc.
- Janssen Biotech Inc.
- Novartis AG
- Academy of Finland (AKA) [312074, 331671, 285380, 334229, 334229, 312074, 285380, 331671] Funding Source: Academy of Finland (AKA)
- H2020 Societal Challenges Programme [667301] Funding Source: H2020 Societal Challenges Programme
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The study utilized Finnish national hospital and biobank databases to link MUC5B variant with increased risk of RA-ILD. In patients with RA, MUC5B promoter variant was also identified as a strong risk factor for ILD.
Objectives To estimate lifetime risk of developing rheumatoid arthritis-associated interstitial lung disease (RA-ILD) with respect to the strongest known risk factor for pulmonary fibrosis, a MUC5B promoter variant. Methods FinnGen is a collection of epidemiological cohorts and hospital biobank samples, integrating genetic data with up to 50 years of follow-up within nationwide registries in Finland. Patients with RA and ILD were identified from the Finnish national hospital discharge, medication reimbursement and cause-of-death registries. We estimated lifetime risks of ILD by age 80 with respect to the common variant rs35705950, a MUC5B promoter variant. Results Out of 293 972 individuals, 1965 (0.7%) developed ILD by age 80. Among all individuals in the dataset, MUC5B increased the risk of ILD with a HR of 2.44 (95% CI: 2.22 to 2.68). Out of 6869 patients diagnosed with RA, 247 (3.6%) developed ILD. In patients with RA, MUC5B was a strong risk factor of ILD with a HR similar to the full dataset (HR: 2.27, 95% CI: 1.75 to 2.95). In patients with RA, lifetime risks of ILD were 16.8% (95% CI: 13.1% to 20.2%) for MUC5B carriers and 6.1% (95% CI: 5.0% to 7.2%) for MUC5B non-carriers. The difference between risks started to emerge at age 65, with a higher risk among men. Conclusion Our findings provide estimates of lifetime risk of RA-ILD based on MUC5B mutation carrier status, demonstrating the potential of genomics for risk stratification of RA-ILD.
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