Abstract 12389: Epigenome-Wide Study Identifies Novel Methylation Loci Associated With Body Mass Index and Waist Circumference
Introduction: Body mass index (BMI) and waist circumference (WC) are complex heritable traits with direct implications for human health. An emerging body of evidence links epigenetic processes such as DNA methylation to gene regulation and obesity phenotypes.
Hypothesis: We hypothesized that methylation patterns across the genome are associated with variation in adiposity traits, specifically BMI and WC.
Methods: To identify specific genomic regions that play a role in the epigenetics of obesity, we quantified epigenome-wide DNA methylation in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in 991 European American participants of the Genetics of Lipid Lowering Drugs and Diet Network. We subsequently conducted association analyses, modeling percent methylation at individual cytosine-phosphate-guanine (CpG) sites as a function of BMI and WC, adjusting for age, gender, study site, T-cell purity, smoking, and family structure.
Results: We found epigenome-wide significant associations between eight CpG sites and BMI and five CpG sites and WC, and successfully replicated the top hits in whole blood samples from 2,377 European American participants of the Framingham Heart Study and 2,105 African American participants of the Atherosclerosis Risk in Communities study. Top findings were located in CPT1A (meta-analysis P= 3.5x10-37 for BMI and P=2.2x10-16 for WC), PHGDH (meta-analysis P= 4.7x10-15 for BMI and 2.2x10-8 for WC), CD38 (meta-analysis P= 3.7x10-11 for BMI and 6.1x10-13 for WC) and long intergenic non-coding RNA 00263 (meta-analysis P= 1.2x10-13 for BMI and 5.8x10-10 for WC), regions with biologically plausible relationships to adiposity.
Conclusions: This large-scale epigenome-wide study identified novel robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications.
Author Disclosures: S. Aslibekyan: None. E.W. Demerath: None. M. Mendelson: None. D. Zhi: None. W. Guan: None. L. Liang: None. J. Sha: None. J.S. Pankow: None. C. Liu: None. M. Irvin: None. M. Fornage: None. B. Hidalgo: None. L. Lin: None. K.C. Stanton Thibeault: None. J. Bressler: None. M.Y. Tsai: None. M.L. Grove: None. P.N. Hopkins: None. E. Boerwinkle: None. I.B. Borecki: None. J.M. Ordovas: None. D. Levy: None. H.K. Tiwari: None. D.M. Absher: None. D.K. Arnett: None.
- © 2014 by American Heart Association, Inc.