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整合脂质组学和基因组学:理解心血管疾病的新兴工具。

Integrating lipidomics and genomics: emerging tools to understand cardiovascular diseases.

机构信息

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, PO Box 20, 00014, Helsinki, Finland.

Department of Public Health, Clinicum, University of Helsinki, Helsinki, Finland.

出版信息

Cell Mol Life Sci. 2021 Mar;78(6):2565-2584. doi: 10.1007/s00018-020-03715-4. Epub 2021 Jan 15.

DOI:10.1007/s00018-020-03715-4
PMID:33449144
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8004487/
Abstract

Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity worldwide leading to 31% of all global deaths. Early prediction and prevention could greatly reduce the enormous socio-economic burden posed by CVDs. Plasma lipids have been at the center stage of the prediction and prevention strategies for CVDs that have mostly relied on traditional lipids (total cholesterol, total triglycerides, HDL-C and LDL-C). The tremendous advancement in the field of lipidomics in last two decades has facilitated the research efforts to unravel the metabolic dysregulation in CVDs and their genetic determinants, enabling the understanding of pathophysiological mechanisms and identification of predictive biomarkers, beyond traditional lipids. This review presents an overview of the application of lipidomics in epidemiological and genetic studies and their contributions to the current understanding of the field. We review findings of these studies and discuss examples that demonstrates the potential of lipidomics in revealing new biology not captured by traditional lipids and lipoprotein measurements. The promising findings from these studies have raised new opportunities in the fields of personalized and predictive medicine for CVDs. The review further discusses prospects of integrating emerging genomics tools with the high-dimensional lipidome to move forward from the statistical associations towards biological understanding, therapeutic target development and risk prediction. We believe that integrating genomics with lipidome holds a great potential but further advancements in statistical and computational tools are needed to handle the high-dimensional and correlated lipidome.

摘要

心血管疾病(CVDs)是全球范围内导致 31%全球死亡人数的主要死亡和发病原因。早期预测和预防可以大大减轻 CVDs 带来的巨大社会经济负担。血浆脂质一直是 CVDs 预测和预防策略的核心,这些策略主要依赖于传统脂质(总胆固醇、总甘油三酯、HDL-C 和 LDL-C)。在过去二十年中,脂质组学领域的巨大进展促进了研究工作,以揭示 CVD 中的代谢失调及其遗传决定因素,从而能够理解病理生理机制并识别预测生物标志物,而不仅仅是传统脂质。

本篇综述介绍了脂质组学在流行病学和遗传学研究中的应用及其对该领域当前认识的贡献。我们回顾了这些研究的发现,并讨论了一些例子,这些例子表明了脂质组学在揭示传统脂质和脂蛋白测量无法捕捉的新生物学方面的潜力。这些研究的有希望的发现为 CVD 的个性化和预测医学领域带来了新的机会。

综述进一步讨论了将新兴基因组学工具与高维脂质组学相结合的前景,以从统计学关联转向生物学理解、治疗靶点开发和风险预测。我们相信,将基因组学与脂质组学相结合具有很大的潜力,但需要进一步改进统计和计算工具,以处理高维且相关的脂质组学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73e0/11072536/e7aee61c16e5/18_2020_3715_Fig5_HTML.jpg
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