AUTHOR=Ye Ding , Huang Huijun , Wu David J. H. , Zhang Wanting , Zhou Feixiang , Qian Yu , Zheng Jusheng , Mao Yingying 

TITLE=Association Between Circulating Linoleic Acid and Risk of Ischemic Stroke

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.582623

DOI=10.3389/fgene.2020.582623

ISSN=1664-8021

ABSTRACT=<sec><title>Background</title><p>Observational studies have shown an inverse association between circulating linoleic acid (LA) and risk of ischemic stroke (IS).</p></sec><sec><title>Objective</title><p>The 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.</p></sec><sec><title>Methods</title><p>LA-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.</p></sec><sec><title>Results</title><p>We 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 <italic>P</italic> = 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 <italic>P</italic> = 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.</p></sec><sec><title>Conclusion</title><p>Our study supports a potential inverse association of genetically predicted circulating LA levels with risk of IS, particularly LAS.</p></sec>