Introduction: Carotenoids, which are a reliable biomarker of fruit and vegetable consumption, are positively associated with the lipid profile. Circulating carotenoid concentrations may interact with several omics profiles including genome, transcriptome, and epigenome. Few studies have used multi-omics approaches, and they rarely include environmental factors, such as diet. Objective: The objective of this observational study was to examine the potential role of multi-omics data in the interconnection between diet, represented by total carotenoids, and lipid profile using weighted gene correlation network analysis (WGCNA). Methods: Blood leukocyte DNA methylation levels of 472,245 CpG sites and whole blood gene expression levels of 18,160 transcripts were tested for associations with total carotenoid concentrations using regressions in 48 healthy subjects. WGCNA was used to identify co-omics modules and hub genes related to the lipid profile. Results: Among genes associated with total carotenoid concentrations, a total of 236 genes were identified at both DNA methylation and gene expression levels. Using WGCNA, six modules, consisting of groups of highly correlated genes represented by colors, were identified and linked to the lipid profile. Probes clustered in the turquoise and green modules correlated with plasma lipid concentrations. A total of 28 hub genes were identified. Conclusions: Genome-wide DNA methylation and gene expression levels were both associated with plasma total carotenoid concentrations. Several hub genes, mostly involved in lipid metabolism and inflammatory response with several genetic variants associated with plasma lipid concentrations, came out of the integrative analysis. This provides a comprehensive understanding of the interactive molecular system between carotenoids, omics, and plasma lipid profile.

中文翻译：

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血浆类胡萝卜素浓度和脂质分布之间联系中多组学数据的综合网络分析

简介：类胡萝卜素是一种可靠的水果和蔬菜消费生物标志物，与脂质特征呈正相关。循环类胡萝卜素浓度可能与多种组学特征相互作用，包括基因组、转录组和表观基因组。很少有研究使用多组学方法，也很少包括饮食等环境因素。目的：这项观察性研究的目的是使用加权基因相关网络分析 (WGCNA) 检查多组学数据在饮食（以总类胡萝卜素为代表）和脂质谱之间相互关联中的潜在作用。方法：血液白细胞 DNA 甲基化水平为 472,245 个 CpG 位点，全血基因表达水平为 18，在 48 名健康受试者中使用回归测试了 160 份转录本与总类胡萝卜素浓度的关联。WGCNA 用于识别与脂质谱相关的联合组学模块和中心基因。结果：在与总类胡萝卜素浓度相关的基因中，在 DNA 甲基化和基因表达水平上共鉴定出 236 个基因。使用 WGCNA，确定了由颜色表示的高度相关基因组组成的六个模块，并将其与脂质谱相关联。聚集在绿松石和绿色模块中的探针与血浆脂质浓度相关。共鉴定了 28 个中枢基因。结论：全基因组 DNA 甲基化和基因表达水平均与血浆总类胡萝卜素浓度相关。几个枢纽基因，主要参与脂质代谢和炎症反应，具有与血浆脂质浓度相关的几种遗传变异，来自综合分析。这提供了对类胡萝卜素、组学和血浆脂质特征之间相互作用的分子系统的全面了解。