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Li Chen PhD, Li Chen PhD Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Hubei Key Laboratory of Lipid Chemistry and Nutrition, and Key Laboratory of Oilseeds Processing, Ministry of Agriculture, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Wuhan, 430062 Hubei, China Search for more papers by this author Tianqi Tan PhD Institute of Maternal and Child Health, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430015 China Search for more papers by this author Yashu Chen PhD Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Hubei Key Laboratory of Lipid Chemistry and Nutrition, and Key Laboratory of Oilseeds Processing, Ministry of Agriculture, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Wuhan, 430062 Hubei, China Search for more papers by this author Feipeng Cui PhD Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China Search for more papers by this author Huimin Chen PhD Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China Search for more papers by this author Ying Zhao PhD School of Public Health, Kunming Medical University, Kunming, 650500 China Search for more papers by this author Yuhan Tang PhD Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China Search for more papers by this author Xia Xiang PhD Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Hubei Key Laboratory of Lipid Chemistry and Nutrition, and Key Laboratory of Oilseeds Processing, Ministry of Agriculture, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Wuhan, 430062 Hubei, China Search for more papers by this author Corresponding Author Qianchun Deng PhD Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Hubei Key Laboratory of Lipid Chemistry and Nutrition, and Key Laboratory of Oilseeds Processing, Ministry of Agriculture, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Wuhan, 430062 Hubei, China Address correspondence via email to Qianchun Deng at [emailprotected]. Search for more papers by this author
Li Chen PhD, Li Chen PhD Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Hubei Key Laboratory of Lipid Chemistry and Nutrition, and Key Laboratory of Oilseeds Processing, Ministry of Agriculture, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Wuhan, 430062 Hubei, China Search for more papers by this author Tianqi Tan PhD Institute of Maternal and Child Health, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430015 China Search for more papers by this author Yashu Chen PhD Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Hubei Key Laboratory of Lipid Chemistry and Nutrition, and Key Laboratory of Oilseeds Processing, Ministry of Agriculture, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Wuhan, 430062 Hubei, China Search for more papers by this author Feipeng Cui PhD Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China Search for more papers by this author Huimin Chen PhD Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China Search for more papers by this author Ying Zhao PhD School of Public Health, Kunming Medical University, Kunming, 650500 China Search for more papers by this author Yuhan Tang PhD Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 China Search for more papers by this author Xia Xiang PhD Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Hubei Key Laboratory of Lipid Chemistry and Nutrition, and Key Laboratory of Oilseeds Processing, Ministry of Agriculture, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Wuhan, 430062 Hubei, China Search for more papers by this author Corresponding Author Qianchun Deng PhD Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, Hubei Key Laboratory of Lipid Chemistry and Nutrition, and Key Laboratory of Oilseeds Processing, Ministry of Agriculture, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory, Wuhan, 430062 Hubei, China Address correspondence via email to Qianchun Deng at [emailprotected]. Search for more papers by this author
First published: 12 May 2025
A graphical abstract can be found in the online acricle at http://onlinelibrary.wiley.com/doi/10.1002/art.43229/abs.
Author disclosures are available at https://onlinelibrary.wiley.com/doi/10.1002/art.43229.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/art.43229.
Abstract
Objective
To investigate the associations of polyunsaturated fatty acids (PUFAs) intakes with rheumatoid arthritis (RA) risk, alongside the role of genetic predisposition and the potential mediating effects of circulating proteins.
Methods
Utilizing data from 188,597 RA-free participants in the UK Biobank, Cox proportional hazard models assessed the association of PUFAs intakes with RA risk. The polygenic risk score for RA further allowed evaluation of genetic predisposition's modifying effects. Olink proteomics identified protein signatures associated with PUFAs intakes and RA risk, with mediation analyses highlighting specific proteins as potential mediators.
Results
Over a median follow-up for 9.1 years, 1,640 RA cases were documented. Each one-standard deviation increase in the intakes of stearidonic acid (SDA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) reduced RA risk by 9%-10%. Among individuals with high genetic risk, n-3 PUFAs intakes (including SDA, EPA, DPA, and DHA) significantly decreased RA risk, with antagonistic additive interactions against genetic predisposition. Olink-based proteomic analysis displayed that RA risk and specific n-3 PUFAs intakes (DHA, DPA, and SDA) were primarily associated with immune response and inflammation, cytokine interactions, signal transduction, cell adhesion and migration, and metabolic pathways. Mediation analyses identified 55 mediating proteins involved in immune regulation, inflammation, and cell homeostasis. Notably, CD80 and TNFRSF4 emerged as vital mediators in the relationship between specific n-3 PUFAs intakes and RA risk.
Conclusion
These findings indicated the potential benefits of n-3 PUFAs intakes in reducing RA risk and provided new insights into the mechanisms by which n-3 PUFAs influence RA risk.
Accepted Articles
Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future.
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