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Plasma lipid levels and risk of retinal vascular occlusion: A genetic study using Mendelian randomization

The causal effects of plasma lipid levels and the risk of retinal vascular occlusion (RVO) have not been clearly identified, especially for high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C). Here, we try to identify these causal risk factors using a two-sam...

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Autores principales: Zheng, Changwei, Lin, Yi, Jiang, Bingcai, Zhu, Xiaomin, Lin, Qianyi, Luo, Wangdu, Tang, Min, Xie, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9588969/
https://www.ncbi.nlm.nih.gov/pubmed/36299452
http://dx.doi.org/10.3389/fendo.2022.954453
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author Zheng, Changwei
Lin, Yi
Jiang, Bingcai
Zhu, Xiaomin
Lin, Qianyi
Luo, Wangdu
Tang, Min
Xie, Lin
author_facet Zheng, Changwei
Lin, Yi
Jiang, Bingcai
Zhu, Xiaomin
Lin, Qianyi
Luo, Wangdu
Tang, Min
Xie, Lin
author_sort Zheng, Changwei
collection PubMed
description The causal effects of plasma lipid levels and the risk of retinal vascular occlusion (RVO) have not been clearly identified, especially for high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C). Here, we try to identify these causal risk factors using a two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms (SNPs) were chosen as instrumental variables (IVs). We obtained genetic variants associated with lipid exposure at the genome-wide significance (P<5×10(−8)) level from a meta-analysis of GWAS from the Global Lipids Genetics Consortium (GLGC) based on 188,577 individuals of mostly European ancestry for MR analyses. Meanwhile, we used lipid GWAS from UK Biobank (UKB) with a sample size of 115,078 individuals as a supplement. We obtained genetic predictors of RVO from a FinnGen biobank study. We conducted both univariable and multivariable MR (MVMR) analyses to identify the causal effects of RVO. Although inverse variance weighted (IVW) was the primary method used for MR analyses, MR–Egger and weighted-median methods were used as supplements to IVW. We determined the heterogeneity of IVs using Cochrane’s Q test and I(2) , and used the MR–Egger intercept and MR-PRESSO Global test to detect horizontal pleiotropy. A leave-one-out sensitivity analysis was conducted by removing a single variant from the analysis. Genetically predicted increased HDL-C level was associated with decreased risk of RVO from GLGC [OR=0.806; 95% CI=(0.659, 0.986); P=0.036], which was consistent with UKB results [OR=0.766; 95% CI=(0.635, 0.925); P=0.005]. MVMR analysis for plasma lipids [adjusted OR=0.639; 95% CI=(0.411, 0.992); P=0.046] or diabetes [adjusted OR=0.81; 95% CI=(0.67, 0.979); P=0.029] suggested that low HDL-C may be an independent risk factor for RVO. However, there was no evidence to support a causal association between LDL-C {GLGC [adjusted OR=1.015; 95% CI=(0.408, 2.523); P=0.975], UKB [OR=1.115; 95% CI=(0.884, 1.407); P=0.359]}, total cholesterol {GLGC [adjusted OR=0.904; 95% CI=(0.307, 2.659); P=0.854], UKB [OR=1.047; 95% CI=(0.816, 1.344); P=0.716]} or triglycerides {GLGC [OR=1.103; 95% CI=(0.883, 1.378); P=0.385], UKB [OR=1.003; 95% CI=(0.827, 1.217); P=0.098]} and RVO. Using two-sample MR analysis, our study suggested that dyslipidemia was a risk factor for RVO. Furthermore, our results indicated that a low HDL-C level may be an independent risk factor for RVO, suggesting that controlling HDL-C level may be effective in RVO development.
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spelling pubmed-95889692022-10-25 Plasma lipid levels and risk of retinal vascular occlusion: A genetic study using Mendelian randomization Zheng, Changwei Lin, Yi Jiang, Bingcai Zhu, Xiaomin Lin, Qianyi Luo, Wangdu Tang, Min Xie, Lin Front Endocrinol (Lausanne) Endocrinology The causal effects of plasma lipid levels and the risk of retinal vascular occlusion (RVO) have not been clearly identified, especially for high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C). Here, we try to identify these causal risk factors using a two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms (SNPs) were chosen as instrumental variables (IVs). We obtained genetic variants associated with lipid exposure at the genome-wide significance (P<5×10(−8)) level from a meta-analysis of GWAS from the Global Lipids Genetics Consortium (GLGC) based on 188,577 individuals of mostly European ancestry for MR analyses. Meanwhile, we used lipid GWAS from UK Biobank (UKB) with a sample size of 115,078 individuals as a supplement. We obtained genetic predictors of RVO from a FinnGen biobank study. We conducted both univariable and multivariable MR (MVMR) analyses to identify the causal effects of RVO. Although inverse variance weighted (IVW) was the primary method used for MR analyses, MR–Egger and weighted-median methods were used as supplements to IVW. We determined the heterogeneity of IVs using Cochrane’s Q test and I(2) , and used the MR–Egger intercept and MR-PRESSO Global test to detect horizontal pleiotropy. A leave-one-out sensitivity analysis was conducted by removing a single variant from the analysis. Genetically predicted increased HDL-C level was associated with decreased risk of RVO from GLGC [OR=0.806; 95% CI=(0.659, 0.986); P=0.036], which was consistent with UKB results [OR=0.766; 95% CI=(0.635, 0.925); P=0.005]. MVMR analysis for plasma lipids [adjusted OR=0.639; 95% CI=(0.411, 0.992); P=0.046] or diabetes [adjusted OR=0.81; 95% CI=(0.67, 0.979); P=0.029] suggested that low HDL-C may be an independent risk factor for RVO. However, there was no evidence to support a causal association between LDL-C {GLGC [adjusted OR=1.015; 95% CI=(0.408, 2.523); P=0.975], UKB [OR=1.115; 95% CI=(0.884, 1.407); P=0.359]}, total cholesterol {GLGC [adjusted OR=0.904; 95% CI=(0.307, 2.659); P=0.854], UKB [OR=1.047; 95% CI=(0.816, 1.344); P=0.716]} or triglycerides {GLGC [OR=1.103; 95% CI=(0.883, 1.378); P=0.385], UKB [OR=1.003; 95% CI=(0.827, 1.217); P=0.098]} and RVO. Using two-sample MR analysis, our study suggested that dyslipidemia was a risk factor for RVO. Furthermore, our results indicated that a low HDL-C level may be an independent risk factor for RVO, suggesting that controlling HDL-C level may be effective in RVO development. Frontiers Media S.A. 2022-10-10 /pmc/articles/PMC9588969/ /pubmed/36299452 http://dx.doi.org/10.3389/fendo.2022.954453 Text en Copyright © 2022 Zheng, Lin, Jiang, Zhu, Lin, Luo, Tang and Xie https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Endocrinology
Zheng, Changwei
Lin, Yi
Jiang, Bingcai
Zhu, Xiaomin
Lin, Qianyi
Luo, Wangdu
Tang, Min
Xie, Lin
Plasma lipid levels and risk of retinal vascular occlusion: A genetic study using Mendelian randomization
title Plasma lipid levels and risk of retinal vascular occlusion: A genetic study using Mendelian randomization
title_full Plasma lipid levels and risk of retinal vascular occlusion: A genetic study using Mendelian randomization
title_fullStr Plasma lipid levels and risk of retinal vascular occlusion: A genetic study using Mendelian randomization
title_full_unstemmed Plasma lipid levels and risk of retinal vascular occlusion: A genetic study using Mendelian randomization
title_short Plasma lipid levels and risk of retinal vascular occlusion: A genetic study using Mendelian randomization
title_sort plasma lipid levels and risk of retinal vascular occlusion: a genetic study using mendelian randomization
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9588969/
https://www.ncbi.nlm.nih.gov/pubmed/36299452
http://dx.doi.org/10.3389/fendo.2022.954453
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