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Published in: Clinical Rheumatology 5/2022

01-05-2022 | Rheumatoid Arthritis | Original Article

Mendelian randomization study on the causal effects of omega-3 fatty acids on rheumatoid arthritis

Authors: Gaizhi Zhu, Shan Zhou, Yaqi Xu, Ran Gao, Huan Li, Bing Zhai, Xiaoling Liu, Youdi He, Xiaoqian Wang, Gencheng Han, Wenting Su, Renxi Wang

Published in: Clinical Rheumatology | Issue 5/2022

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Abstract

Objectives

To resolve the ongoing debate on the role of plasma omega-3 fatty acids in rheumatoid arthritis (RA), we attempted to identify the association between omega-3 intake and the risk of RA.

Methods

We analyzed data from the largest genome-wide association study (GWAS) for omega-3 fatty acids (N = 114,999 of European ancestry) and RA (14,361 cases and 43,923 controls of European ancestry). Mendelian randomization-egger_intercept, MR-PRESSO, and Cochran’s Q test were used to determine pleiotropy and heterogeneity. Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode were used to evaluate the causal association of plasma omega-3 levels on RA.

Results

We found no significant pleiotropy, heterogeneity, and bias among the omega-3 genetic instrumental variables (IVs) in RA GWAS datasets. MR analysis demonstrated that as omega-3 levels genetically increased, the risk of MS increased using MR-egger (Beta = 0.137, p = 0.037; OR = 1.146, 95% CI: [1.014, 1.296]), weighted median (Beta = 0.162, p = 0.001; OR = 1.176, 95% CI: [1.070, 1.292]), IVW (Beta = 0.102, p = 0.025; OR = 1.108, 95% CI: [1.013, 1.211]), simple mode (Beta = 0.219, p = 0.149; OR = 1.245, 95% CI: [0.931, 1.665]), and weighted mode (Beta = 0.146, p = 0.006; OR = 1.157, 95% CI: [1.051, 1.274]).

Conclusions

Our analysis suggested a causal association between genetically increased plasma omega-3 levels and the increased risk of RA in populations with European ancestry. Thus, to reduce the risk of RA, those of European descent should reduce omega-3 intake.
Key Points
• No significant pleiotropy or heterogeneity among the omega-3 genetic IVs in RA GWAS datasets.
• Genetically increased plasma omega-3 levels enhanced the risk of RA in European lineages.
Appendix
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Metadata
Title
Mendelian randomization study on the causal effects of omega-3 fatty acids on rheumatoid arthritis
Authors
Gaizhi Zhu
Shan Zhou
Yaqi Xu
Ran Gao
Huan Li
Bing Zhai
Xiaoling Liu
Youdi He
Xiaoqian Wang
Gencheng Han
Wenting Su
Renxi Wang
Publication date
01-05-2022
Publisher
Springer International Publishing
Published in
Clinical Rheumatology / Issue 5/2022
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-022-06052-y

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