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

Whitney L Do; Eric A Whitsel; Ricardo Costeira; Olatz M Masachs; Caroline I Le Roy; Jordana T Bell; Lisa R Staimez; Aryeh D Stein; Alicia K Smith; Steve Horvath; Themistocles L Assimes; Simin Liu; JoAnn E Manson; Aladdin H Shadyab; Yun Li; Lifang Hou; Parveen Bhatti; Kristina Jordahl; K M Venkat Narayan; Karen N Conneely

doi:10.1093/ije/dyaa215

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

Int J Epidemiol. 2021 May 17;50(2):675-684. doi: 10.1093/ije/dyaa215.

Authors

Whitney L Do^{1

2}, Eric A Whitsel³, Ricardo Costeira⁴, Olatz M Masachs⁴, Caroline I Le Roy⁴, Jordana T Bell⁴, Lisa R Staimez¹, Aryeh D Stein¹, Alicia K Smith⁵, Steve Horvath⁶, Themistocles L Assimes⁷, Simin Liu⁸, JoAnn E Manson⁹, Aladdin H Shadyab¹⁰, Yun Li^{11

12

13}, Lifang Hou¹⁴, Parveen Bhatti^{15

16}, Kristina Jordahl¹⁶, K M Venkat Narayan¹, Karen N Conneely¹⁷

Affiliations

¹ Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
² Nutrition and Health Sciences Program, Laney Graduate School, Emory University, Atlanta, GA, USA.
³ Departments of Epidemiology and Medicine, University of North Carolina, Chapel Hill, NC, USA.
⁴ Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.
⁵ Department of Gynecology and Obstetrics, School of Medicine, Emory University, Atlanta, GA, USA.
⁶ Department of Human Genetics, University of California, Los Angeles, CA, USA.
⁷ Department of Medicine, Stanford University, Palo Alto, CA, USA.
⁸ Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA.
⁹ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁰ Department of Family Medicine and Public Health, University of California San Diego School of Medicine, La Jolla, CA, USA.
¹¹ Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
¹² Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA.
¹³ Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA.
¹⁴ Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
¹⁵ Cancer Control Research, BC Cancer, Vancouver, BC, Canada.
¹⁶ Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹⁷ Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, USA.

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.

Keywords: EWAS; Epigenome; Women’s Health Initiative; diet quality; dietary epigenetics.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

CpG Islands / genetics
DNA Methylation
Diet
Epigenesis, Genetic*
Epigenome*
Female
Genome-Wide Association Study
Humans
Proteins
Women's Health

Substances

Proteins
SEL1L protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding