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      Educational Attainment and Ischemic Stroke: A Mendelian Randomization Study

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          Abstract

          Observational studies have evaluated the potential association of socioeconomic factors such as higher education with the risk of stroke but reported controversial findings. The objective of our study was to evaluate the potential causal association between higher education and the risk of stroke. Here, we performed a Mendelian randomization analysis to evaluate the potential association of educational attainment with ischemic stroke (IS) using large-scale GWAS datasets from the Social Science Genetic Association Consortium (SSGAC, 293,723 individuals), UK Biobank (111,349 individuals), and METASTROKE consortium (74,393 individuals). We selected three Mendelian randomization methods including inverse-variance-weighted meta-analysis (IVW), weighted median regression, and MR–Egger regression. IVW showed that each additional 3.6-year increase in years of schooling was significantly associated with a reduced IS risk (OR = 0.54, 95% CI: 0.41–0.71, and p = 1.16 × 10 –5). Importantly, the estimates from weighted median (OR = 0.49, 95% CI: 0.33–0.73, and p = 1.00 × 10 –3) and MR–Egger estimate (OR = 0.18, 95% CI: 0.06–0.60, and p = 5.00 × 10 –3) were consistent with the IVW estimate in terms of direction and magnitude. In summary, we provide genetic evidence that high education could reduce IS risk.

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          Most cited references51

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          UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age

          Cathie Sudlow and colleagues describe the UK Biobank, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.
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            Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases

            Horizontal pleiotropy occurs when the variant has an effect on disease outside of its effect on the exposure in Mendelian randomization (MR). Violation of the ‘no horizontal pleiotropy’ assumption can cause severe bias in MR. We developed the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test to identify horizontal pleiotropic outliers in multi-instrument summary-level MR testing. We showed using simulations that MR-PRESSO is best suited when horizontal pleiotropy occurs in <50% of instruments. Next, we applied MR-PRESSO, along with several other MR tests to complex traits and diseases, and found that horizontal pleiotropy: (i) was detectable in over 48% of significant causal relationships in MR; (ii) introduced distortions in the causal estimates in MR that ranged on average from −131% to 201%; (iii) induced false positive causal relationships in up to 10% of relationships; and (iv) can be corrected in some but not all instances.
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              Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians

              Mendelian randomisation uses genetic variation as a natural experiment to investigate the causal relations between potentially modifiable risk factors and health outcomes in observational data. As with all epidemiological approaches, findings from Mendelian randomisation studies depend on specific assumptions. We provide explanations of the information typically reported in Mendelian randomisation studies that can be used to assess the plausibility of these assumptions and guidance on how to interpret findings from Mendelian randomisation studies in the context of other sources of evidence
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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                11 February 2022
                2021
                : 12
                : 794820
                Affiliations
                [1] 1 Department of Neurology , Tianjin Fourth Central Hospital , The Fourth Central Hospital Affilicated to Nankai University , The Fourth Central Clinical College of Tianjin Medical University , Tianjin, China
                [2] 2 Taishan Academy of Medical Sciences , Taian City Central Hospital , Taian, China
                [3] 3 Second Affiliated Hospital , Brain Science Institute , Key Laboratory of Cerebral Microcirculation in Universities of Shandong , Shandong First Medical University and Shandong Academy of Medical Sciences , Taian, China
                [4] 4 Department of Cardiovascular , Tianjin Fourth Central Hospital , The Fourth Central Hospital Affilicated to Nankai University , The Fourth Central Clinical College of Tianjin Medical University , Tianjin, China
                Author notes

                Edited by: Liangcai Zhang, Janssen Research and Development, United States

                Reviewed by: Yang Hu, Harbin Institute of Technology, China

                Keshen Li, The First Affiliated Hospital of Jinan University, China

                *Correspondence: Mingfeng Yang, mfyang@ 123456163.com ; Huanming Li, 13820788663@ 123456163.com

                This article was submitted to Statistical Genetics and Methodology, a section of the journal Frontiers in Genetics

                Article
                794820
                10.3389/fgene.2021.794820
                8876515
                35222520
                68510feb-d7e4-4f4b-b054-9a0e74819dca
                Copyright © 2022 Gao, Wang, Ni, Fan, Zhao, Huang, Yang and Li.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 October 2021
                : 24 December 2021
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: 81871855
                Categories
                Genetics
                Original Research

                Genetics
                stroke,educational attainment,mendelian randomization,genome-wide association studies,ischaemic stroke

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