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Associations of Lipids and Lipid-Lowering Drugs with Risk of Vascular Dementia: A Mendelian Randomization Study
Accumulating observational studies suggested that hypercholesterolemia is associated with vascular dementia (VaD); however, the causality between them remains unclear. Hence, the aim of this study is to infer causal associations of circulating lipid-related traits [including high-density lipoprotein...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9824558/ https://www.ncbi.nlm.nih.gov/pubmed/36615727 http://dx.doi.org/10.3390/nu15010069 |
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author | Zhang, Xiaoyu Geng, Tao Li, Ning Wu, Lijuan Wang, Youxin Zheng, Deqiang Guo, Bo Wang, Baoguo |
author_facet | Zhang, Xiaoyu Geng, Tao Li, Ning Wu, Lijuan Wang, Youxin Zheng, Deqiang Guo, Bo Wang, Baoguo |
author_sort | Zhang, Xiaoyu |
collection | PubMed |
description | Accumulating observational studies suggested that hypercholesterolemia is associated with vascular dementia (VaD); however, the causality between them remains unclear. Hence, the aim of this study is to infer causal associations of circulating lipid-related traits [including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A-I (apoA-I), and apolipoprotein B (apoB)] with VaD jointly using univariable MR (uvMR), multivariable MR (mvMR) and bidirectional two-sample MR methods. Then, the summary-data-based MR (SMR) and two-sample MR analysis were conducted to investigate the association of lipid-lowering drugs target genes expression (including HMGCR, PCSK9, NPC1L1, and APOB) and LDL-C level mediated by these target genes with VaD. The results of forward MR analyses found that genetically predicted HDL-C, LDL-C, TG, apoA-I, and apoB concentrations were not significantly associated with the risk of VaD (all p > 0.05). Notably, there was suggestive evidence for a causal effect of genetically predicted VaD on HDL-C via reverse MR analysis [odds ratio (OR), 0.997; 95% confidence interval (CI), 0.994–0.999; p = 0.022]. On the contrary, the MR results showed no significant relationship between VaD with LDL-C, TG, apoA-I, and apoB. The results for the SMR method found that there was no evidence of association for expression of HMGCR, PCSK9, NPC1L1, and APOB gene with risk of VaD. Furthermore, the result of MR analysis provided evidence for the decreased LDL-C level mediated by gene HMGCR reduced the risk of VaD (OR, 18.381; 95% CI, 2.092–161.474; p = 0.009). Oppositely, none of the IVW methods indicated any causal effects for the other three genes. Using genetic data, this study provides evidence that the VaD risk may cause a reduction of HDL-C level. Additionally, the finding supports the hypothesis that lowering LDL-C levels using statins may be an effective prevention strategy for VaD risk, which requires clinical trials to confirm this result in the future. |
format | Online Article Text |
id | pubmed-9824558 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98245582023-01-08 Associations of Lipids and Lipid-Lowering Drugs with Risk of Vascular Dementia: A Mendelian Randomization Study Zhang, Xiaoyu Geng, Tao Li, Ning Wu, Lijuan Wang, Youxin Zheng, Deqiang Guo, Bo Wang, Baoguo Nutrients Article Accumulating observational studies suggested that hypercholesterolemia is associated with vascular dementia (VaD); however, the causality between them remains unclear. Hence, the aim of this study is to infer causal associations of circulating lipid-related traits [including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A-I (apoA-I), and apolipoprotein B (apoB)] with VaD jointly using univariable MR (uvMR), multivariable MR (mvMR) and bidirectional two-sample MR methods. Then, the summary-data-based MR (SMR) and two-sample MR analysis were conducted to investigate the association of lipid-lowering drugs target genes expression (including HMGCR, PCSK9, NPC1L1, and APOB) and LDL-C level mediated by these target genes with VaD. The results of forward MR analyses found that genetically predicted HDL-C, LDL-C, TG, apoA-I, and apoB concentrations were not significantly associated with the risk of VaD (all p > 0.05). Notably, there was suggestive evidence for a causal effect of genetically predicted VaD on HDL-C via reverse MR analysis [odds ratio (OR), 0.997; 95% confidence interval (CI), 0.994–0.999; p = 0.022]. On the contrary, the MR results showed no significant relationship between VaD with LDL-C, TG, apoA-I, and apoB. The results for the SMR method found that there was no evidence of association for expression of HMGCR, PCSK9, NPC1L1, and APOB gene with risk of VaD. Furthermore, the result of MR analysis provided evidence for the decreased LDL-C level mediated by gene HMGCR reduced the risk of VaD (OR, 18.381; 95% CI, 2.092–161.474; p = 0.009). Oppositely, none of the IVW methods indicated any causal effects for the other three genes. Using genetic data, this study provides evidence that the VaD risk may cause a reduction of HDL-C level. Additionally, the finding supports the hypothesis that lowering LDL-C levels using statins may be an effective prevention strategy for VaD risk, which requires clinical trials to confirm this result in the future. MDPI 2022-12-23 /pmc/articles/PMC9824558/ /pubmed/36615727 http://dx.doi.org/10.3390/nu15010069 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Xiaoyu Geng, Tao Li, Ning Wu, Lijuan Wang, Youxin Zheng, Deqiang Guo, Bo Wang, Baoguo Associations of Lipids and Lipid-Lowering Drugs with Risk of Vascular Dementia: A Mendelian Randomization Study |
title | Associations of Lipids and Lipid-Lowering Drugs with Risk of Vascular Dementia: A Mendelian Randomization Study |
title_full | Associations of Lipids and Lipid-Lowering Drugs with Risk of Vascular Dementia: A Mendelian Randomization Study |
title_fullStr | Associations of Lipids and Lipid-Lowering Drugs with Risk of Vascular Dementia: A Mendelian Randomization Study |
title_full_unstemmed | Associations of Lipids and Lipid-Lowering Drugs with Risk of Vascular Dementia: A Mendelian Randomization Study |
title_short | Associations of Lipids and Lipid-Lowering Drugs with Risk of Vascular Dementia: A Mendelian Randomization Study |
title_sort | associations of lipids and lipid-lowering drugs with risk of vascular dementia: a mendelian randomization study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9824558/ https://www.ncbi.nlm.nih.gov/pubmed/36615727 http://dx.doi.org/10.3390/nu15010069 |
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