Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 53 2 2024 01 30 397 403 EN Xiaowen Hou School of Public Health, Shenyang Medical College, Shenyang, 110034, China Jiaqi Zheng School of Public Health, Shenyang Medical College, Shenyang, 110034, China Jiajun Zhang School of Public Health, Shenyang Medical College, Shenyang, 110034, China Lin Tao School of International Education, Shenyang Medical College, Shenyang, 110034, China Kaiwen Cen School of Public Health, Shenyang Medical College, Shenyang, 110034, China Ying Cui School of Public Health, Shenyang Medical College, Shenyang, 110034, China Ji Wu School of Public Health, Shenyang Medical College, Shenyang, 110034, China 2023 05 10 2023 08 12 Background: Ischemic stroke (IS) is the leading cause of disability and mortality worldwide. Low-density lipoprotein cholesterol (LDL-C) levels hadno potential risk on ischemic stroke. However, higher LDL-C levels were closely related to IS. Based on two antagonistic viewpoints, a Mendelian randomization (MR) study was designed to evaluate the causal effects of LDL-C levels on IS. Methods: Datasets of LDL-C levels and ischemic stroke were acquired from genome-wide association studies (GWAS). Weighted median method was conducted for main analysis, and MR-Egger and inverse-variance weighted (IVW) methods were performed for auxiliary analyses. Heterogeneity and pleiotropic tests were utilized to confirm the reliability of this study. Results: A total of 359 single nucleotide polymorphisms (SNPs) were associated with LDL-C levels (P < 5 × 10−8) and 337 SNPs were available in ischemic stroke with eliminating outliers. LDL-C levels were significantly associated with ischemic stroke (OR = 1.104, 95%CI = 1.019 - 1.195, P = 1.52 × 10-2). MR-Egger and IVW showed directionally similar estimates (MR-Egger: OR = 1.120, 95%CI = 1.040 - 1.207, P = 3.12 × 10-3; IVW: OR = 1.120, 95%CI = 1.064 - 1.178, P = 1.17 × 10-5). Conclusion: LDL-C levels had causal effects on IS, providing insights into the design of future interventions to reduce the burden of ischemic stroke. https://ijph.tums.ac.ir/index.php/ijph/article/view/31975 https://ijph.tums.ac.ir/index.php/ijph/article/download/31975/8165