BACKGROUND: Observational studies have shown an inverse association between circulating linoleic acid (LA) and risk of ischemic stroke (IS). OBJECTIVE: 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. METHODS: 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. RESULTS: 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 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. CONCLUSION: Our study supports a potential inverse association of genetically predicted circulating LA levels with risk of IS, particularly LAS.
BACKGROUND: Observational studies have shown an inverse association between circulating linoleic acid (LA) and risk of ischemic stroke (IS). OBJECTIVE: 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. METHODS: 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. RESULTS: 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 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. CONCLUSION: Our study supports a potential inverse association of genetically predicted circulating LA levels with risk of IS, particularly LAS.
Authors: Tom M Palmer; Jonathan A C Sterne; Roger M Harbord; Debbie A Lawlor; Nuala A Sheehan; Sha Meng; Raquel Granell; George Davey Smith; Vanessa Didelez Journal: Am J Epidemiol Date: 2011-05-09 Impact factor: 4.897
Authors: Jie Zheng; Denis Baird; Maria-Carolina Borges; Jack Bowden; Gibran Hemani; Philip Haycock; David M Evans; George Davey Smith Journal: Curr Epidemiol Rep Date: 2017-11-22
Authors: Johannes Kettunen; Ayşe Demirkan; Peter Würtz; Harmen H M Draisma; Toomas Haller; Rajesh Rawal; Anika Vaarhorst; Antti J Kangas; Leo-Pekka Lyytikäinen; Matti Pirinen; René Pool; Antti-Pekka Sarin; Pasi Soininen; Taru Tukiainen; Qin Wang; Mika Tiainen; Tuulia Tynkkynen; Najaf Amin; Tanja Zeller; Marian Beekman; Joris Deelen; Ko Willems van Dijk; Tõnu Esko; Jouke-Jan Hottenga; Elisabeth M van Leeuwen; Terho Lehtimäki; Evelin Mihailov; Richard J Rose; Anton J M de Craen; Christian Gieger; Mika Kähönen; Markus Perola; Stefan Blankenberg; Markku J Savolainen; Aswin Verhoeven; Jorma Viikari; Gonneke Willemsen; Dorret I Boomsma; Cornelia M van Duijn; Johan Eriksson; Antti Jula; Marjo-Riitta Järvelin; Jaakko Kaprio; Andres Metspalu; Olli Raitakari; Veikko Salomaa; P Eline Slagboom; Melanie Waldenberger; Samuli Ripatti; Mika Ala-Korpela Journal: Nat Commun Date: 2016-03-23 Impact factor: 14.919