Abstract
BackgroundObservational studies have shown an inverse association between circulating linoleic acid (LA) and risk of ischemic stroke (IS).ObjectiveThe aim of this study was to explore whether genetic variants predicting levels of circulating LA are associated with IS and its subtypes using a two-sample Mendelian randomization (MR) analysis.MethodsLA-related single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of 8,631 participants, and summary statistics of IS and IS subtypes were obtained from the MEGASTROKE consortium. MR analysis was performed using the inverse-variance weighted (IVW) method complemented with other approaches, including weighted-median, weighted-mode, MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression, to test for the robustness of the association. Moreover, we conducted bidirectional MR analysis to assess the impact of IS-associated SNPs on circulating LA levels. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.ResultsWe found that genetically predicted circulating LA levels were inversely associated with the risk of IS by the IVW method (OR = 0.98, 95% CI: 0.97–0.99, and P = 0.003). Subgroup analyses showed a statistically significant association between LA and risk of large artery stroke (LAS; OR = 0.95, 95% CI: 0.92–0.98, and P = 0.004), but not for other IS subtypes. The results were stable in sensitivity analyses, and no evidence of reverse association between LA and risk of IS, or LAS was observed.ConclusionOur study supports a potential inverse association of genetically predicted circulating LA levels with risk of IS, particularly LAS.
Highlights
Stroke is one of the leading causes of mortality and disability worldwide (Hankey, 2017)
In the primary Mendelian randomization (MR) analyses, we found that genetically predicted circulating Linoleic acid (LA) levels were inversely associated with risk of Ischemic stroke (IS) (OR: 0.98, 95% confidence intervals (95% CIs): 0.97–0.99, and P = 0.003)
Genetically predicted circulating LA was associated with a reduced risk of large artery stroke (LAS) (OR: 0.95, 95% CI: 0.92–0.98, and P = 0.004; Table 1)
Summary
Stroke is one of the leading causes of mortality and disability worldwide (Hankey, 2017). Linoleic acid (LA) is one of the primary dietary omega-6. Linoleic Acid and Ischemic Stroke polyunsaturated fatty acids essential for various physiological functions, such as cell signaling and lipid metabolism (Whelan and Fritsche, 2013). Observational studies have reported an inverse relationship between circulating LA level and IS. An individuallevel pooled analysis of 21 cohort studies from 13 countries demonstrated that higher circulating LA level was associated with a lower risk of incident IS (Marklund et al, 2019). Because of the presence of potential confounding and reverse causality in observational studies, it is difficult to distinguish whether the observed association between circulating LA and IS risk is causal or not. Observational studies have shown an inverse association between circulating linoleic acid (LA) and risk of ischemic stroke (IS)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
