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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Abstract: Background: Rheumatoid arthritis (RA) is associated with diverse extra-articular manifestations, including interstitial lung disease (ILD). No previous studies have examined the bidirectional relationship between RA and ILD using the Mendelian randomization (MR) analyses. Therefore, we aimed to investigate this subject using a two-sample bidirectional MR method. Methods: We performed bidirectional two-sample MR using summary statistics from genome-wide association studies (GWASs). The data are publicly available, de-identified, and from European (EUR) and East Asian (EAS) ancestries. Results: A total of 474,450 EUR participants and 351,653 EAS participants were included for either forward or reverse MR analysis. In our primary analysis, we found significant evidence of an increased risk of ILD associated with RA among individuals of EUR ancestry (ORMR-cML = 1.08; 95% confidence interval [CI] = 1.03–1.14; p = 0.003) and EAS ancestry (ORMR-cML = 1.37; 95% CI = 1.23–1.54; p < 0.001). Additionally, the reverse MR showed significant evidence of an increased risk of RA associated with ILD among those of EUR ancestry (ORMR-cML = 1.12; 95% CI = 1.05–1.19; p < 0.001). However, only one instrumental variable was selected in the EAS ILD GWAS, and there was no increased risk of RA associated with ILD in those of EAS ancestry (ORMR-cML = 1.02; 95% CI = 0.91–1.14; p = 0.740). Conclusions: Our findings indicate that RA and ILD have a bidirectional causal inference when using the MR analysis of GWAS datasets. The findings are only relevant for genetic predisposition; thus, further research is needed to determine the impact of non-genetic predispositions.

Details

Title
Multi-Ancestry Causal Association between Rheumatoid Arthritis and Interstitial Lung Disease: A Bidirectional Two-Sample Mendelian Randomization Study
Author
Bo-Guen Kim 1   VIAFID ORCID Logo  ; Yoon, Sanghyuk 2 ; Sun Yeop Lee 2   VIAFID ORCID Logo  ; Kim, Eun Gyo 2 ; Jung Oh Kim 2   VIAFID ORCID Logo  ; Kim, Jong Seung 3 ; Lee, Hyun 4   VIAFID ORCID Logo 

 Division of Pulmonary Medicine, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea; [email protected] 
 Basgenbio Inc., Seoul 04167, Republic of Korea; [email protected] (S.Y.); [email protected] (E.G.K.); [email protected] (J.O.K.) 
 Department of Medical Informatics, Jeonbuk National University, Jeonju 54907, Republic of Korea; Department of Otorhinolaryngology, Jeonbuk National University, Jeonju 54907, Republic of Korea 
 Division of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea 
First page
6080
Publication year
2024
Publication date
2024
Publisher
MDPI AG
e-ISSN
20770383
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3120675665
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.