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Session: Personalizing Nutrition - Select Genetic, Epigenetic and Microbiome Interactions Influencing Diet and Diet-related Diseases (Oral 13)

(OR13-01-23) Epigenetic Signature of Dietary and Lifestyle Factors on Obesity

Sunday, July 23, 2023

4:00 PM – 4:12 PM ET

Location: Constitution B

Presenting Author(s)

Chao-Qiang Lai, PhD

Molecular Biologist
USDA ARS, Nutrition and Genomics, Jean Mayer USDA Human Nutrition Research Center
Boston, Massachusetts, United States

Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

Co-Author(s)

YL

Yu-Chi Lee

USDA Agricultural Research Service
HZ

Haihan Zeng

JM-USDA Human Nutrition Research Ctr on Aging @ Tufts
LP

Laurence Parnell, Ph. D.

USDA ARS, JM-USDA Human Nutrition Research Ctr on Aging @ Tufts
Boston, Massachusetts, United States
CS

Caren Smith

JM-USDA Human Nutrition Research Ctr on Aging @ Tufts
NM

Nicola M. McKeown, M. McKeown

Department of Health Sciences, Sargent College of Health and Rehabilitation Sciences, Boston University
JM

Jiantao Ma, Ph.D.

Assistant Professor Division of Nutrition Data Science
Nutrition Epidemiology and Data Science, Friedman School of Nutrition Science and Policy at Tufts University
Boston, Massachusetts, United States
DA

Donna Arnett

University of South Carolina, Columbia
JO

José M. Ordovás, Phd

Tufts University
Boston, Massachusetts, United States

Disclosure(s):

Chao-Qiang Lai, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: Obesity is a global health concern with contributions from multiple factors, including diet, lifestyle, genetic, and epigenetic variation. Epigenetic status such as DNA methylation profiles influenced by environmental exposures affect human health. The epigenetic roles of underlying effects of diet and other lifestyle choices on obesity outcomes remain to be elucidated. The study objective was to map DNA methylation marks associated with diet and lifestyle habits contributing to obesity.

Methods: We first conducted an epigenome-wide association study (EWAS) to identify epigenetic markers, DNA methylation sites (DMSs) associated with obesity-related traits, body mass index (BMI) and waist circumference (WC) in the Framingham Heart Study (FHS) Offspring population (n=2,262). We next determined the relationships between the identified obesity-associated DMSs and dietary and lifestyle factors (collected over 13 years). Third, we employed mediation analyses to assess the effects of identified dietary/lifestyle variables on obesity via DMSs as mediators. Lastly, we validated our findings in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study.

Results: In FHS, EWAS revealed 124 BMI- or WC-associated DMSs in 92 gene regions, including ABCG1, DHCR24, RPS6KA2, CPT1A, LINC00263, ABAT, KIAA0664, and PHGDH. We found 278 significant associations between 65 DMSs and one or more dietary and lifestyle-related variables. Mediation analyses further showed that alcohol use, carbohydrate consumption, and dietary quality scores significantly impacted obesity outcomes mediated through DMSs, such as cg06690548 in SLC7A11, cg18120259 in LOC100132354, cg00574958 in CPT1A, and cg19693031 in TXNIP. Moreover, dietary fat positively affected obesity traits mediated by DMSs, including cg07504977 and cg00574958 in CPT1A. Results from the GOLDN further support our findings.

Conclusions: Our results suggest that dietary intakes and lifestyle choices such as dietary composition, diet quality, and alcohol use could affect obesity risk via epigenetic changes in DNA methylation.

Funding Sources: This work was funded by the US Department of Agriculture, under agreement no. 8050-51000-107-000D.