Predicting the causal relationship between polyunsaturated fatty acids and cerebral aneurysm risk from a Mendelian randomization study

Author:

Yu Weijie12,Mei Yunyun3,Li Chongfei12,Lu Zhenwei12,Chen Xiaoyu4,Yu Hao4,Chen Xiaoyan5,Huang Qionghui16,Li Zhangyu2,Xiao Deyong2,Zhou Liwei2,Wang Zhanxian2ORCID

Affiliation:

1. The School of Clinical Medicine, Fujian Medical University

2. Department of Neurosurgery, Department of Neurosurgery Quality Control Center, The First Affiliated Hospital of Xiamen University, Xiamen Key Laboratory of Brain Center

3. Department of Neurosurgery, Fudan University Shanghai Cancer Center Xiamen Hospital

4. School of Medicine, Xiamen University

5. Internal medicine, The First Affiliated Hospital of Xiamen University

6. Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, Xiamen Key Laboratory of Brain Center

Abstract

No conclusive evidence for a link between polyunsaturated fatty acids (PUFA) and cerebral aneurysm has been found in observational research. The aim of our study was to determine the causal impact of PUFA on cerebral aneurysm.Two sample Mendelian randomization (MR) was performed using genetic instruments derived from a recent genome wide association study (GWAS) of fatty acids from UK Biobank and outcome data obtained from the large-scale cerebral aneurysm GWASs in European ancestry which include IA, aneurysmal subarachnoid hemorrhage (aSAH) and unruptured intracranial aneurysm (uIA). Sensitivity analyses were implemented with MR-Egger intercept test, MR-PRESSO, leave-one-out analysis and so on. Bayesian colocalization (COLOC) methods was conducted to focus on the association between the fatty acid gene expression and cerebral aneurysm.Genetically predicted assessed omega-3 fatty acids decreased the risk for IA (OR = 0.80, 95% CI: 0.69 - 0.91, P = 1.01ⅹ10 -3 ) and aSAH (OR = 0.71, 95% CI: 0.61 - 0.84, P = 3.73ⅹ10 -5 ). Furthermore, the Docosahexaenoic acid decreased the risk for IA (OR = 0.75, 95% CI: 0.63 - 0.87, P = 3.12ⅹ10 -4 ) and aSAH (OR = 0.67, 95% CI: 0.55 - 0.8, P = 2.32ⅹ10 -5 ). The same results were discovered from ratio of omega-3 fatty acids to total fatty acids. While the ratio of omega-6 fatty acids to omega-3 fatty acids increased the risk of IA (OR = 1.27, 95% CI: 1.12 – 1.44, P = 1.53ⅹ10 -4 ) and aSAH (OR = 1.35, 95% CI: 1.17 – 1.56, P = 5.78ⅹ10 -5 ). The result of the COLOC suggested that the above four kinds of fatty acids and IA, aSAH likely share causal variants in gene fatty acid desaturase 2, separately.This study utilized integrative analysis of MR and colocalization to discover causal relationships between genetic variants, PUFA and cerebral aneurysm.This study was funded by the Natural Science Foundation of China (82072777), the Natural Science Foundation of Xiamen (3502Z20227097), Fujian Provincial Health Commission, Provincial Health and Health Young and Middle-aged Backbone Talent Training Project (2022GGB010).

Publisher

eLife Sciences Publications, Ltd

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