scholarly journals Epigenome-wide association study of diet quality in the Women’s Health Initiative and TwinsUK cohort

Author(s):  
Whitney L Do ◽  
Eric A Whitsel ◽  
Ricardo Costeira ◽  
Olatz M Masachs ◽  
Caroline I Le Roy ◽  
...  

Abstract Background Diet quality is a risk factor for chronic disease and mortality. Differential DNA methylation across the epigenome has been associated with chronic disease risk. Whether diet quality is associated with differential methylation is unknown. This study assessed whether diet quality was associated with differential DNA methylation measured across 445 548 loci in the Women’s Health Initiative (WHI) and the TwinsUK cohort. Design The discovery cohort consisted of 4355 women from the WHI. The replication cohort consisted of 571 mono- and dizygotic twins from the TwinsUK cohort. DNA methylation was measured in whole blood using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). A meta-analysis, stratified by study cohort, was performed using generalized linear models that regressed methylation on AHEI-2010, adjusting for cell composition, chip number and location, study characteristics, principal components of genetic relatedness, age, smoking status, race/ethnicity and body mass index (BMI). Statistical significance was defined as a false discovery rate < 0.05. Significant sites were tested for replication in the TwinsUK cohort, with significant replication defined by P < 0.05 and a consistent direction. Results Diet quality was significantly associated with differential DNA methylation at 428 cytosine-phosphate-guanine (CpG) sites in the discovery cohort. A total of 24 CpG sites were consistent with replication in the TwinsUK cohort, more than would be expected by chance (P = 2.7x10-4), with one site replicated in both the blood and adipose tissue (cg16379999 located in the body of SEL1L). Conclusions Diet quality was associated with methylation at 24 CpG sites, several of which have been associated with adiposity, inflammation and dysglycaemia. These findings may provide insight into pathways through which diet influences chronic disease.

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
R Whitney Leet ◽  
Eric Whitsel ◽  
Lisa Staimez ◽  
Steve Horvath ◽  
Themistocles Assimes ◽  
...  

Abstract Objectives This study examined the influence of diet on the methylome by analyzing 428,019 cytosine-guanine nucleotide pair (CpG) sites and assessing whether diet quality was associated with differential methylation patterns. Methods The study population included 4529 women from the Women's Health Initiative (WHI) observation and clinical trial from three ancillary studies: EMPC, BAA23, and AS311. DNA methylation was measured from whole blood samples using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). An epigenome-wide association study (EWAS) meta-analysis, stratified by study cohort, was done using generalized linear models by regressing methylation β values (β = Methylated probes/[Methylated + Unmethylated probes]) for each CpG site on the primary exposure, AHEI, adjusting for cell composition, chip number and location, study characteristics, principle components of genetic relatedness, age, ethnicity and BMI. Significance was set at Holm-Bonferroni P < 0.05. Results Demographic characteristics are described by quartile of AHEI with Quartile 4 equivalent to the healthiest diet (highest score) and Quartile 1 equivalent to the poorest diet (lowest score) in Table 1. We found diet quality was significantly associated with 340 CpG sites after false discovery correction (Figure 1). While statistically significant, effect sizes were small (∼0.0003). These findings suggest that, on average, as AHEI increases by one SD (10.1 units), methylation changes by only ±0.003 in associated CpG sites. When examining the top 20 CpG sites (Table 2), several sites were located in genes critical to metabolism, including cg26137868 in the FOXA2 gene and cg20006924 in the RORA gene, both related to the regulation of glucose and fat metabolism and 3 CpG sites in the SLC18A2, SLC2A14, and SLC16A3 genes related to nutrient transport. Conclusions This is the first reported EWAS examining the relationship between diet quality and methylation in humans. While diet quality was statistically associated with many CpG sites, the effect sizes were small. Further investigation is required to understand the relationship between diet quality and the methylome. Funding Sources NA. Supporting Tables, Images and/or Graphs


2014 ◽  
Vol 114 (7) ◽  
pp. 1036-1045 ◽  
Author(s):  
Melanie D. Hingle ◽  
Betsy C. Wertheim ◽  
Hilary A. Tindle ◽  
Lesley Tinker ◽  
Rebecca A. Seguin ◽  
...  

2014 ◽  
Vol 106 (11) ◽  
pp. dju314-dju314 ◽  
Author(s):  
C. A. Thomson ◽  
T. E. Crane ◽  
B. C. Wertheim ◽  
M. L. Neuhouser ◽  
W. Li ◽  
...  

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