Abstract

Background and aimsDiet may alter gene expression in immune cells involved in atherosclerotic cardiovascular disease susceptibility. However, we still lack a robust understanding of the association between diet and immune cell-related gene expression in humans. Therefore, we examined associations between dietary patterns (DPs) and gene expression profiles in peripheral blood mononuclear cells (PBMCs) in a population of healthy, Norwegian adults (n = 130 women and 105 men). Methods and resultsWe used factor analysis to define a posteriori DPs from food frequency questionnaire-based dietary assessment data. In addition, we derived interpretable features from microarray-based gene expression data (13 967 transcripts) using two algorithms: CIBERSORT for estimation of cell subtype proportions, and weighted gene co-expression network analysis (WGCNA) for cluster discovery. Finally, we associated DPs with either CIBERSORT-predicted PBMC leukocyte distribution or WGCNA gene clusters using linear regression models. We detected three DPs that broadly reflected Western, Vegetarian, and Low carbohydrate diets. CIBERSORT-predicted percentage of monocytes associated negatively with the Vegetarian DP. For women, the Vegetarian DP associated with a large gene cluster consisting of 600 genes mainly involved in regulation of DNA transcription, whereas for men, the Western DP inversely associated with a smaller cluster of 36 genes mainly involved in regulation of metabolic and inflammatory processes. A subsequent protein–protein interaction network analysis suggested that genes within these clusters might physically interact in biological networks. ConclusionsAlthough the present findings are exploratory, our analysis pipeline serves as a useful framework for studying the association between diet and gene expression.

Highlights

  • Atherosclerotic cardiovascular disease (ASCVD) is one of the main causes of death worldwide [1]

  • The Vegetarian dietary pattern (DP) associated with a large gene cluster consisting of 600 genes mainly involved in regulation of DNA transcription, whereas for men, the Western DP inversely associated with a smaller cluster of 36 genes mainly involved in regulation of metabolic and inflammatory processes

  • We describe in detail the statistical and bioinformatic analyses related to DPs, gene expression clusters, and statistical modeling

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Summary

Introduction

Atherosclerotic cardiovascular disease (ASCVD) is one of the main causes of death worldwide [1] It is mainly caused by life-long exposure to classical risk factors such as obesity, hypertension, dyslipidemia and dysglycemia [2]. A posteriori DPs may constitute robust measures of global diet exposure, and could be used to strengthen the reliability of associations between diet and biomarkers within a population This may be especially relevant in order to examine highvariance biomarkers such as gene expression profiles. We still lack a robust understanding of the association between diet and immune cell-related gene expression in humans. We examined associations between dietary patterns (DPs) and gene expression profiles in peripheral blood mononuclear cells (PBMCs) in a population of healthy, Norwegian adults (n Z 130 women and 105 men).

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