Article Text
Abstract
Objectives The genetic background of rheumatoid arthritis–interstitial lung disease (RA-ILD) has been evaluated in Europeans, but little knowledge has been obtained in non-Europeans. This study aimed to elucidate genome-wide risk of RA-ILD in non-Europeans.
Methods We performed an initial genome-wide association study (GWAS) of RA-ILD in the Japanese population. By conducting the meta-analysis of the three GWAS datasets of the RA cohorts and biobank of Japanese, our study included 358 RA-ILD cases and 4550 RA subjects without ILD. We then conducted the stratified analysis of the effect of the GWAS risk allele in each CT image pattern.
Results We identified one novel RA-ILD risk locus at 7p21 that satisfied the genome-wide significance threshold (rs12702634 at RPA3-UMAD1, OR=2.04, 95% CI 1.59 to 2.60, p=1.5×10−8). Subsequent stratified analysis based on the CT image patterns demonstrated that the effect size of the RA-ILD risk allele (rs12702634-C) was large with the UIP pattern (OR=1.86, 95% CI 0.97 to 3.58, p=0.062) and the probable UIP pattern (OR=2.26, 95% CI 1.36 to 3.73, p=0.0015).
Conclusion We revealed one novel genetic association with RA-ILD in Japanese. The RA-ILD risk of the identified variant at RPA3-UMAD1 was relatively high in the CT image patterns related to fibrosis. Our study should contribute to elucidation of the complicated aetiology of RA-ILD.
- pulmonary fibrosis
- rheumatoid arthritis
- gene polymorphism
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Footnotes
Handling editor Josef S Smolen
YS and SH contributed equally.
Contributors YS and YO designed the study and wrote the manuscripts. YS, MK and YK performed the analysis. SH, KI, TM, ET and MH constructed the clinical and genotype data. YT, AK and YO supervised the study.
Funding This research was supported by AMED under Grant Numbers JP19ek0410041 and JP20ek0410075, Takeda Science Foundation and Bioinformatics Initiative of Osaka University Graduate School of Medicine, Osaka University. MK was supported by a Nakajima Foundation Fellowship and the Masason Foundation.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval This study was approved by the ethical committee of Osaka University.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request. GWAS genotype data from the BBJ subjects are deposited at National Bioscience Database Center Human Database (Research ID: hum0014).