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Title: Healthy diet is associated with gene expression in blood: the Framingham Heart Study

Author
item LIN, HONGHUANG - Boston University
item ROGERS, GAIL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LUNETTA, KATHRYN - Boston University
item LEVY, DANIEL - National Institutes Of Health (NIH)
item MIAO, XIAO - Shanghai University
item TROY, LISA - University Of Massachusetts
item JACQUES, PAUL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item MURABITO, JOANNE - Boston University

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/18/2019
Publication Date: 6/12/2020
Citation: Lin, H., Rogers, G.T., Lunetta, K.L., Levy, D., Miao, X., Troy, L.M., Jacques, P.F., Murabito, J.M. 2020. Healthy diet is associated with gene expression in blood: the Framingham Heart Study. American Journal of Clinical Nutrition. 110(3):742-749. https://doi.org/10.1093/ajcn/nqz060.
DOI: https://doi.org/10.1093/ajcn/nqz060

Interpretive Summary: Consumption of a healthy diet is associated with significant reduction in cardiovascular disease, cancer, type 2 diabetes and longevity. One means by which a healthy diet may influence both disease and longevity is through regulation of the expression of genes involved in metabolic and nutrient signaling pathways. Gene expression refers to the process by which the information contained in our DNA is converted via RNA (transcription) to form a functional gene product, typically a protein (translation). The Dietary Guidelines for Americans (DGA) represents recommendations for a healthy dietary pattern developed to help Americans make healthy food and beverage choices. The objectives of our study were to examine the relation between consumption of a healthy diet consistent with the DGA recommendations and gene expression in a community-based adult cohort and to explore potential molecular mechanisms linking diet with health. We used the 2015 Dietary Guidelines for Americans Adherence Index (DGAI) score to quantify key dietary recommendations of the 2015 DGA. Our current analyses included 2220 participants from the Framingham Heart Study second generation (mean age 66+/-9, 55.4% women) and 2941 third generation (mean age 46+/-9, 54.5% women) cohorts. DGAI was significantly associated with the expression of 19 genes. The gene most strongly associated with the DGAI score was one that is a regulator of obesity and energy expenditure. Next we created a gene score weighting the 19 genes based on strongly their expression was related to the DGAI and we observed that this gene score predicated several metabolic traits including BMI, fasting glucose level, metabolic syndrome, and prevalence and incidence of type 2 diabetes. In conclusion, our study found a healthier diet pattern was significantly associated with the expression of 19 gene, and that the expression profile of these genes was also associated with several metabolic traits suggesting potential molecular mechanisms for future investigation linking healthy diets with better health outcomes in older adults.

Technical Abstract: Background: Genes in metabolic and nutrient signaling pathways play important roles in lifespan in model organisms and human longevity. Objective: We examined the relation of a quantitative measure of healthy diet to gene expression in a community-based cohort. Design: We used the 2015 Dietary Guidelines for Americans Adherence Index (DGAI) score to quantify key dietary recommendations of an overall healthy diet. Our current analyses included 2220 Offspring participants (mean age 66+/-9, 55.4% women) and 2941 Third Generation participants (mean age 46+/-9, 54.5% women) from the Framingham Heart Study. Gene expression was profiled in blood using the Affymetrix Human Exon 1.0 ST Array. We conducted a transcriptome-wide association study of DGAI adjusting for age, sex, smoking, cell counts, and technical covariates. We also constructed a combined gene score from genes significantly associated with DGAI. Results: The DGAI was significantly associated with the expression of 19 genes (false discovery rate <0.05). The most significant gene, ARRDC3, is a member of the arrestin family of proteins and evidence in animal models and human data suggests that this gene is a regulator of obesity and energy expenditure. The DGAI gene score was associated with BMI (P=1.4x10^-50), fasting glucose level (P=2.5x10^-11), type 2 diabetes (P=1.1x10^-5) and metabolic syndrome (P=1.8x10^-32). Conclusion: Healthier diet was associated with genes involved in metabolic function. Further work is needed to replicate our findings and investigate the relation of a healthy diet to altered gene regulation.