Assessment of causal relationships between omega-3 and omega-6 polyunsaturated fatty acids in autoimmune rheumatic diseases: a brief research report from a Mendelian randomization study Provisionally Accepted

Xiao Xu¹ Xu Xu² Mohammad A. Zakeri³ Shu-Yun Wang⁴ Min Yan⁵ Yuan-Hong Wang⁶ Li Li⁶ Zhi-Ling Sun⁷ Rong-Yun Wang⁸ Lin-Zhong Miao^9*

• ¹Nantong Health College of Jiangsu Province, China
• ²Renmin Hospital of Wuhan University, China
• ³Rafsanjan University of Medical Sciences, Iran
• ⁴St. Paul University Manila, Philippines
• ⁵Changzhou University, China
• ⁶Third Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, China
• ⁷Nanjing University of Chinese Medicine, China
• ⁸Zhejiang Chinese Medical University, China
• ⁹Suzhou University, China

Background: Currently, the association between the consumption of polyunsaturated fatty acids (PUFAs) and the susceptibility to autoimmune rheumatic diseases (ARDs) remains conflict and lacks substantial evidence in various clinical studies. To address this issue, we employed Mendelian randomization (MR) to establish causal links between six types of PUFAs and their connection to the risk of ARDs.We retrieved summary-level data on six types of PUFAs, and five different types of ARDs from publicly accessible GWAS statistics. Causal relationships were determined using a two-sample MR analysis, with the IVW approach serving as the primary analysis method. To ensure the reliability of our research findings, we used four complementary approaches and conducted multivariable MR analysis (MVMR). Additionally, we investigated reverse causality through a reverse MR analysis.Our results indicate that a heightened genetic predisposition for elevated levels of EPA (ORIVW: 0.924, 95% CI: 0.666-1.283, PIVW =0.025) was linked to a decreased susceptibility to psoriatic arthritis (PsA). These findings suggest that EPA supplementation may be a promising strategy for preventing PsA onset. Further well-powered epidemiological studies and clinical trials are warranted to explore the potential mechanisms underlying the protective effects of EPA in PsA.