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Effect of n-3 polyunsaturated fatty acids on ischemic heart disease and cardiometabolic risk factors: a two-sample Mendelian randomization study

BACKGROUND: The cardioprotective ability of n-3 polyunsaturated fatty acids (PUFAs) is controversial. Most studies suggest a specific role for PUFAs in cardioprotection from ischemic heart disease (IHD). However, few studies have used genetic biomarkers of n-3 PUFAs to examine their potential relati...

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Autores principales: Xu, Bayi, Xu, Zhixia, Xu, Duanmin, Tan, Xuerui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576934/
https://www.ncbi.nlm.nih.gov/pubmed/34749668
http://dx.doi.org/10.1186/s12872-021-02342-6
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author Xu, Bayi
Xu, Zhixia
Xu, Duanmin
Tan, Xuerui
author_facet Xu, Bayi
Xu, Zhixia
Xu, Duanmin
Tan, Xuerui
author_sort Xu, Bayi
collection PubMed
description BACKGROUND: The cardioprotective ability of n-3 polyunsaturated fatty acids (PUFAs) is controversial. Most studies suggest a specific role for PUFAs in cardioprotection from ischemic heart disease (IHD). However, few studies have used genetic biomarkers of n-3 PUFAs to examine their potential relationships with IHD. This study aimed to use Mendelian randomization to evaluate whether genetically-predicted n-3 PUFAs affect IHD and cardiometabolic risk factors (CRFs). METHODS: Genetic variants strongly (p < 5 × 10(–8)) and independently (r(2) > 0.1) associated with n-3 PUFAs were derived from the CHARGE Consortium (including 8,866 subjects of European ancestry) and were used as instrumental variables (IVs) for evaluating the effect of n-3 PUFAs, including α-linolenic acid (ALA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Data on the associations between the IVs and IHD, myocardial infarction, and CRFs (including diabetes, lipids, blood pressure, body mass index, and waist-to-hip ratio (WHR)) were obtained from the UK Biobank SOFT CAD GWAS with the CARDIoGRAMplusC4D 1000 Genomes-based GWAS (113,937 IHD cases and 339,115 controls), the Myocardial Infarction Genetics and CARDIoGRAM Exome consortia (42,335 MI cases and 78,240 controls), the DIAbetes Genetics Replication And Meta-analysis consortium (26,676 diabetes mellitus cases and 132,532 controls), the Global Lipids Genetics Consortium (n = 196,475), the International Consortium for Blood Pressure (n = 69,395), and the meta-analysis of GWAS for body fat distribution in the UK Biobank and Genetic Investigation of Anthropometric Traits (n = 694,649). RESULTS: Genetically-predicted higher ALA was associated with lower risk of IHD, type 2 diabetes (T2D), and lower serum lipids. The effect size per 0.05-unit increase (about 1 standard deviation) in plasma ALA level) was − 1.173 (95% confidence interval − 2.214 to − 0.133) for IHD. DPA and EPA had no association with IHD but were associated with a higher risk of T2D, higher levels of lipids or WHR. DHA had no association with IHD or CRFs. CONCLUSIONS: Our study suggests a benefit of ALA for IHD and its main risk factors. DHA, DPA, and EPA had no association with IHD but were partly associated with increasing cardiometabolic risk factors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-021-02342-6.
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spelling pubmed-85769342021-11-10 Effect of n-3 polyunsaturated fatty acids on ischemic heart disease and cardiometabolic risk factors: a two-sample Mendelian randomization study Xu, Bayi Xu, Zhixia Xu, Duanmin Tan, Xuerui BMC Cardiovasc Disord Research Article BACKGROUND: The cardioprotective ability of n-3 polyunsaturated fatty acids (PUFAs) is controversial. Most studies suggest a specific role for PUFAs in cardioprotection from ischemic heart disease (IHD). However, few studies have used genetic biomarkers of n-3 PUFAs to examine their potential relationships with IHD. This study aimed to use Mendelian randomization to evaluate whether genetically-predicted n-3 PUFAs affect IHD and cardiometabolic risk factors (CRFs). METHODS: Genetic variants strongly (p < 5 × 10(–8)) and independently (r(2) > 0.1) associated with n-3 PUFAs were derived from the CHARGE Consortium (including 8,866 subjects of European ancestry) and were used as instrumental variables (IVs) for evaluating the effect of n-3 PUFAs, including α-linolenic acid (ALA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Data on the associations between the IVs and IHD, myocardial infarction, and CRFs (including diabetes, lipids, blood pressure, body mass index, and waist-to-hip ratio (WHR)) were obtained from the UK Biobank SOFT CAD GWAS with the CARDIoGRAMplusC4D 1000 Genomes-based GWAS (113,937 IHD cases and 339,115 controls), the Myocardial Infarction Genetics and CARDIoGRAM Exome consortia (42,335 MI cases and 78,240 controls), the DIAbetes Genetics Replication And Meta-analysis consortium (26,676 diabetes mellitus cases and 132,532 controls), the Global Lipids Genetics Consortium (n = 196,475), the International Consortium for Blood Pressure (n = 69,395), and the meta-analysis of GWAS for body fat distribution in the UK Biobank and Genetic Investigation of Anthropometric Traits (n = 694,649). RESULTS: Genetically-predicted higher ALA was associated with lower risk of IHD, type 2 diabetes (T2D), and lower serum lipids. The effect size per 0.05-unit increase (about 1 standard deviation) in plasma ALA level) was − 1.173 (95% confidence interval − 2.214 to − 0.133) for IHD. DPA and EPA had no association with IHD but were associated with a higher risk of T2D, higher levels of lipids or WHR. DHA had no association with IHD or CRFs. CONCLUSIONS: Our study suggests a benefit of ALA for IHD and its main risk factors. DHA, DPA, and EPA had no association with IHD but were partly associated with increasing cardiometabolic risk factors. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-021-02342-6. BioMed Central 2021-11-08 /pmc/articles/PMC8576934/ /pubmed/34749668 http://dx.doi.org/10.1186/s12872-021-02342-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Xu, Bayi
Xu, Zhixia
Xu, Duanmin
Tan, Xuerui
Effect of n-3 polyunsaturated fatty acids on ischemic heart disease and cardiometabolic risk factors: a two-sample Mendelian randomization study
title Effect of n-3 polyunsaturated fatty acids on ischemic heart disease and cardiometabolic risk factors: a two-sample Mendelian randomization study
title_full Effect of n-3 polyunsaturated fatty acids on ischemic heart disease and cardiometabolic risk factors: a two-sample Mendelian randomization study
title_fullStr Effect of n-3 polyunsaturated fatty acids on ischemic heart disease and cardiometabolic risk factors: a two-sample Mendelian randomization study
title_full_unstemmed Effect of n-3 polyunsaturated fatty acids on ischemic heart disease and cardiometabolic risk factors: a two-sample Mendelian randomization study
title_short Effect of n-3 polyunsaturated fatty acids on ischemic heart disease and cardiometabolic risk factors: a two-sample Mendelian randomization study
title_sort effect of n-3 polyunsaturated fatty acids on ischemic heart disease and cardiometabolic risk factors: a two-sample mendelian randomization study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576934/
https://www.ncbi.nlm.nih.gov/pubmed/34749668
http://dx.doi.org/10.1186/s12872-021-02342-6
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