Gaizhi Zhu1, Shan Zhou1, Yaqi Xu1, Ran Gao1, Huan Li1, Bing Zhai2, Xiaoling Liu3, Youdi He4, Xiaoqian Wang5, Gencheng Han6, Wenting Su7, Renxi Wang8. 1. Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing, 100069, China. 2. Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, 100853, China. 3. Department of Dermatology, First Medical Centre of Chinese, PLA General Hospital, Beijing, 100853, China. 4. Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. 5. Staidson (Beijing) Biopharmaceuticals Co., Ltd, Beijing, 100176, China. 6. Department of Neuroimmune and Antibody Engineering, Beijing Institute of Basic Medical Sciences, Box 130 (3), Taiping Road #27, Beijing, 100850, China. genchenghan@163.com. 7. Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing, 100069, China. wtsu@ccmu.edu.cn. 8. Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing, 100069, China. renxi_wang@ccmu.edu.cn.
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.
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.
Authors: Matthew J Page; Joanne E McKenzie; Patrick M Bossuyt; Isabelle Boutron; Tammy C Hoffmann; Cynthia D Mulrow; Larissa Shamseer; Jennifer M Tetzlaff; Elie A Akl; Sue E Brennan; Roger Chou; Julie Glanville; Jeremy M Grimshaw; Asbjørn Hróbjartsson; Manoj M Lalu; Tianjing Li; Elizabeth W Loder; Evan Mayo-Wilson; Steve McDonald; Luke A McGuinness; Lesley A Stewart; James Thomas; Andrea C Tricco; Vivian A Welch; Penny Whiting; David Moher Journal: BMJ Date: 2021-03-29