University of Oulu

Palomäki A, Palotie A, et al Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutation carriers Annals of the Rheumatic Diseases 2021;80:1530-1536.

Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutation carriers

Saved in:
Author: Palomäki, Antti1,2; FinnGen Rheumatology Clinical Expert Group; Palotie, Aarno2,3,4;
Organizations: 1Centre for Rheumatology and Clinical Immunology, and Department of Medicine, Turku University Hospital and University of Turku, Turku, Finland
2Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
3Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
4Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
5Department of Rheumatology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
6Orton Orthopaedic Hospital, Helsinki, Finland
7Department of Public Health, University of Helsinki, Helsinki, Finland
8Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland
9Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
10Administration Center, Tampere University Hospital, Tampere, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
Persistent link:
Language: English
Published: BMJ, 2021
Publish Date: 2022-08-05


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.

see all

Series: Annals of the rheumatic diseases
ISSN: 0003-4967
ISSN-E: 1468-2060
ISSN-L: 0003-4967
Volume: 80
Pages: 1530 - 1536
DOI: 10.1136/annrheumdis-2021-220698
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by Turku University Hospital Research Foundation (to AnttiP), the Sigrid Jusélius Foundation (to SR and AarnoP); Foundation and the Horizon 2020 Research and Innovation Programme [grant number 667301 (COSYN) to AarnoP]; University of Helsinki HiLIFE Fellow grants 2017-2020 (to SR); Academy of Finland Center of Excellence in Complex Disease Genetics (grant number 312062 to SR, 312074 to AarnoP); Academy of Finland (grant number 331671 to NM, grant number 285380 to SR, 334229 to JK and TL). This study is part of the FinnGen project funded by Business Finland (grant numbers HUS 4685/31/2016 and UH 4386/31/2016) and 12 pharma companies: AbbVie Inc, AstraZeneca UK Ltd, Biogen MA Inc, Celgene Corporation, Celgene International II Sàrl, Genentech Inc, Merck Sharp & Dohme Corp, Pfizer Inc, GlaxoSmithKline Intellectual Property Development Ltd, Sanofi US Services Inc, Maze Therapeutics Inc, Janssen Biotech Inc and Novartis AG.
Copyright information: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ. is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: