Epigenome-wide association study of diet quality in the Women’s Health Initiative and TwinsUK cohort
| Autor: | Whitney L Do, Yun Li, Kristina M. Jordahl, Eric A. Whitsel, Jordana T. Bell, Themistocles L. Assimes, Alicia K. Smith, Caroline I. Le Roy, K.M. Venkat Narayan, Parveen Bhatti, JoAnn E. Manson, Karen N. Conneely, Simin Liu, Lifang Hou, Aladdin H. Shadyab, Ricardo Costeira, Aryeh D. Stein, Steve Horvath, Olatz Mompeo Masachs, Lisa R. Staimez |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Epidemiology 030204 cardiovascular system & hematology Epigenesis Genetic Epigenome 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans Risk factor business.industry Women's Health Initiative Proteins General Medicine Methylation DNA Methylation Diet Miscellaneous 030104 developmental biology CpG site Cohort DNA methylation Women's Health CpG Islands Female business Body mass index Genome-Wide Association Study |
| Zdroj: | Int J Epidemiol |
| ISSN: | 1464-3685 0300-5771 |
| DOI: | 10.1093/ije/dyaa215 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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