Honghuang Lin1,2, Gail T Rogers3, Kathryn L Lunetta1,4, Daniel Levy1,5, Xiao Miao6, Lisa M Troy7, Paul F Jacques3, Joanne M Murabito1,8. 1. National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA. 2. Sections of Computational Biomedicine and. 3. Friedman School of Nutrition Science and Policy and the Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA. 4. Department of Biostatistics, Boston University School of Public Health, Boston, MA. 5. Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. 6. Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 7. Department of Nutrition, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA. 8. General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA.
Abstract
BACKGROUND: Genes in metabolic and nutrient signaling pathways play important roles in lifespan in model organisms and human longevity. OBJECTIVE: The aim of this study was to examine the relation of a quantitative measure of healthy diet to gene expression in a community-based cohort. METHODS: 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 y, 55.4% women) and 2941 Third-Generation participants (mean age 46 ± 9 y, 54.5% women) from the Framingham Heart Study. Gene expression was profiled in blood through the use of 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 body mass index (P = 1.4 × 10-50), fasting glucose concentration (P = 2.5 × 10-11), type 2 diabetes (P = 1.1 × 10-5), and metabolic syndrome (P = 1.8 × 10-32). CONCLUSIONS: 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.
BACKGROUND: Genes in metabolic and nutrient signaling pathways play important roles in lifespan in model organisms and human longevity. OBJECTIVE: The aim of this study was to examine the relation of a quantitative measure of healthy diet to gene expression in a community-based cohort. METHODS: 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 y, 55.4% women) and 2941 Third-Generation participants (mean age 46 ± 9 y, 54.5% women) from the Framingham Heart Study. Gene expression was profiled in blood through the use of 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 body mass index (P = 1.4 × 10-50), fasting glucose concentration (P = 2.5 × 10-11), type 2 diabetes (P = 1.1 × 10-5), and metabolic syndrome (P = 1.8 × 10-32). CONCLUSIONS: 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.
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