Causal and mediating effects of lipid and facial aging: association study integrating GWAS, eQTL, mQTL, and pQTL data.

IF 3.9 2区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Mingjian Zhao, Zhanchen He, Lukuan Liu, Yichen Wang, LinQi Gao, Yuxuan Shang, Mengru Zhu
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引用次数: 0

Abstract

Background: Increasing evidence suggests a potential causal association between lipid levels and facial aging. The aim of this study was to investigate the relationship between levels of specific lipids and facial aging via Mendelian randomization methods. Additionally, this study aimed to identify mediators and explore relevant genes and drug targets.

Methods: In this study, genome-wide association data on plasma lipids from 7,174 Finnish individuals in the UK Biobank were used. Two-sample Mendelian randomization was applied to assess the causal effects of specific lipids on facial aging. Sensitivity and pleiotropy analyses were conducted to ensure the robustness and reliability of the results. Multivariate Mendelian randomization was conducted to account for the potential impact of confounding factors. Furthermore, summary-data-based Mendelian randomization was used to identify relevant genes, which were validated through multiomics data. Finally, drug‒gene interactions were explored via molecular docking techniques.

Results: Two-sample Mendelian randomization analysis revealed a causal relationship between lipid levels and facial aging. According to the multivariate Mendelian randomization results, smoking was found to mediate this association, and these lipids remained significantly associated with facial aging, even after accounting for environmental confounders. Using summary-data-based Mendelian randomization, CYP21A2, CCND1, PSMA4, and MED1 were identified as potential gene targets, with MED1 further validated through pQTL and mQTL data. Additionally, the MED1 protein was found to bind spontaneously with astragalin, fenofibrate, and ginsenoside.

Conclusions: The results revealed a causal relationship between lipid levels and facial aging, revealing key gene targets that were still significantly associated with facial aging after controlling for environmental confounders. Additionally, the interactions between MED1 and certain drugs may indicate potential pathways for therapeutic interventions related to facial aging.

血脂与面部衰老的因果效应和中介效应:整合 GWAS、eQTL、mQTL 和 pQTL 数据的关联研究。
背景:越来越多的证据表明,血脂水平与面部衰老之间可能存在因果关系。本研究旨在通过孟德尔随机方法研究特定血脂水平与面部衰老之间的关系。此外,本研究还旨在确定中介因素并探索相关基因和药物靶点:本研究使用了英国生物库中 7,174 名芬兰人的血浆脂质全基因组关联数据。采用双样本孟德尔随机法评估特定血脂对面部衰老的因果效应。为确保结果的稳健性和可靠性,还进行了敏感性和多向性分析。为了考虑混杂因素的潜在影响,还进行了多变量孟德尔随机分析。此外,还采用了基于汇总数据的孟德尔随机分析法来确定相关基因,并通过多组学数据对这些基因进行了验证。最后,通过分子对接技术探讨了药物与基因之间的相互作用:结果:双样本孟德尔随机分析显示,血脂水平与面部衰老之间存在因果关系。根据多变量孟德尔随机分析结果,发现吸烟是这种关联的中介,即使考虑了环境混杂因素,这些血脂仍与面部衰老显著相关。通过基于汇总数据的孟德尔随机化,CYP21A2、CCND1、PSMA4 和 MED1 被确定为潜在的基因靶标,其中 MED1 通过 pQTL 和 mQTL 数据得到进一步验证。此外,还发现MED1蛋白与黄芪甲素、非诺贝特和人参皂苷自发结合:结论:研究结果揭示了血脂水平与面部衰老之间的因果关系,揭示了在控制环境混杂因素后仍与面部衰老显著相关的关键基因靶点。此外,MED1与某些药物之间的相互作用可能预示着与面部衰老有关的潜在治疗干预途径。
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来源期刊
Lipids in Health and Disease
Lipids in Health and Disease 生物-生化与分子生物学
CiteScore
7.70
自引率
2.20%
发文量
122
审稿时长
3-8 weeks
期刊介绍: Lipids in Health and Disease is an open access, peer-reviewed, journal that publishes articles on all aspects of lipids: their biochemistry, pharmacology, toxicology, role in health and disease, and the synthesis of new lipid compounds. Lipids in Health and Disease is aimed at all scientists, health professionals and physicians interested in the area of lipids. Lipids are defined here in their broadest sense, to include: cholesterol, essential fatty acids, saturated fatty acids, phospholipids, inositol lipids, second messenger lipids, enzymes and synthetic machinery that is involved in the metabolism of various lipids in the cells and tissues, and also various aspects of lipid transport, etc. In addition, the journal also publishes research that investigates and defines the role of lipids in various physiological processes, pathology and disease. In particular, the journal aims to bridge the gap between the bench and the clinic by publishing articles that are particularly relevant to human diseases and the role of lipids in the management of various diseases.
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