Dr. Stella Aslibekyan, assistant professor in the department of epidemiology at the University of Alabama at Birmingham School of Public Health, recently conducted an epigenome-wide analysis of DNA methylation and obesity traits. UAB co-investigators are department colleagues Ms. Jin Sha, statistician; Dr. Ryan Irvin, assistant professor; Dr. Bertha Hidalgo, assistant professor; and Dr. Donna K. Arnett, professor and chair; as well as Dr. Degui Zhi, assistant professor, and Dr. Hemant K. Tiwari, professor, in the department of biostatistics, section on statistical genetics.
The study measured DNA methylation patterns in CD4+ T-cells using the Illumina Infinium HumanMethylation450 array in a total of 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). Methylation is believed to be linked to gene expression, turning genes “up” or “down” in response to environmental stimuli. The GOLDN study modeled methylation at individual cytosine-phosphate-guanine (CpG) sites across the entire genome as a function of body mass index (BMI), while adjusting for age, gender, study site, T-cell purity, smoking, and family relationships. Similar models were fit for waist circumference (WC).
According to the study, epigenome-wide significant associations between eight CpG sites and BMI and five CpG sites and WC were found, replicating the highest hits in whole blood samples from the Framingham Heart Study (n = 2,377) and the Atherosclerosis Risk in Communities Study (n = 2,097); top findings were in “CPT1A (meta-analysis P = 2.7 × 10(-43) for BMI and 9.9 × 10(-23) for WC), PHGDH (meta-analysis P = 2.0 × 10(-15) for BMI and 4.0 × 10(-9) for WC), CD38 (meta-analysis P = 6.3 × 10(-11) for BMI and 1.6 × 10(-12) for WC), and long intergenic non-coding RNA 00263 (meta-analysis P = 2.2 × 10(-16) for BMI and 8.9 × 10(-14) for WC), regions with biologically plausible relationships to adiposity.” For the finding in CPT1A, the methylation status of the region has previously been linked to gene expression and other disease phenotypes such as triglycerides and very low density lipoprotein cholesterol.
“This large-scale epigenome-wide study discovered and replicated robust associations between DNA methylation at CpG loci and obesity indices, laying the groundwork for future diagnostic and/or therapeutic applications,” notes Dr. Aslibekyan.
“Epigenome-wide Study Identifies Novel Methylation Loci Associated with Body Mass Index and Waist Circumference” was published online in July in the journal Obesity,
Journal article: http://www.ncbi.nlm.nih.gov/pubmed/26110892?dopt=Abstract