Abstract

We sought to determine if DNA methylation patterns differed between vegans and non-vegetarians in the Adventist Health Study-2 cohort. Genome-wide DNA methylation derived from buffy coat was profiled in 62 vegans and 142 non-vegetarians. Using linear regression, methylation of CpG sites and genes was categorized or summarized according to various genic/intergenic regions and CpG island-related regions, as well as the promoter. Methylation of genes was measured as the average methylation of available CpG’s annotated to the nominated region of the respective gene. A permutation method defining the null distribution adapted from Storey et al. was used to adjust for false discovery. Differences in methylation of several CpG sites and genes were detected at a false discovery rate < 0.05 in region-specific and overall analyses. A vegan diet was associated predominantly with hypomethylation of genes, most notably methyltransferase-like 1 (METTL1). Although a limited number of differentially methylated features were detected in the current study, the false discovery method revealed that a much larger proportion of differentially methylated genes and sites exist, and could be detected with a larger sample size. Our findings suggest modest differences in DNA methylation in vegans and non-vegetarians, with a much greater number of detectable significant differences expected with a larger sample.

Highlights

  • Findings from the Adventist Health Study-2 (AHS-2) cohort have been prominent among epidemiologic studies linking a vegetarian dietary pattern to lower risks of diabetes, metabolic syndrome, and coronary heart disease [1,2,3,4,5] as well as lower risks of gastrointestinal and prostate cancers, among others [6,7,8]

  • There is some evidence from animal studies and human intervention trials that dietary conditions such as high fat content or caloric restriction may alter genome-wide and gene-specific DNA methylation [24,25,26,27,28,29,30]. It is not clear how habitual dietary patterns differing in consumption of plant- and animal-based foods differ in terms of DNA methylation patterns

  • CpG sites, as well as of CpGs annotated to their respective genes, considering various gene regions, and employing an adapted Storey et al [31,32] permutation method to correct for false discovery

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Summary

Introduction

Findings from the Adventist Health Study-2 (AHS-2) cohort have been prominent among epidemiologic studies linking a vegetarian dietary pattern to lower risks of diabetes, metabolic syndrome, and coronary heart disease [1,2,3,4,5] as well as lower risks of gastrointestinal and prostate cancers, among others [6,7,8]. There is some evidence from animal studies and human intervention trials that dietary conditions such as high fat content or caloric restriction may alter genome-wide and gene-specific DNA methylation [24,25,26,27,28,29,30]. It is not clear how habitual dietary patterns differing in consumption of plant- and animal-based foods differ in terms of DNA methylation patterns. CpG sites, as well as of CpGs annotated to their respective genes (gene methylation), considering various gene regions, and employing an adapted Storey et al [31,32] permutation method to correct for false discovery

Study Population
Laboratory Analysis and Data Processing
Statistical Analyses
Methylation Differences in Vegans and Non-Vegetarians
Differential Methylation of Select Regions Associated with Individual Genes
Differential Methylation of CpG Sites
Discussion
Conclusions
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