Epigenome‐wide study identifies novel methylation loci associated with body mass index and waist circumference. (July 2015)

• Record Type: Journal Article
• Authors: Aslibekyan, Stella; Demerath, Ellen W.; Mendelson, Michael; Zhi, Degui; Guan, Weihua; Liang, Liming; Sha, Jin; Pankow, James S.; Liu, Chunyu; Irvin, Marguerite R.; Fornage, Myriam; Hidalgo, Bertha; Lin, Li‐An; Stanton Thibeault, Krista; Bressler, Jan; Tsai, Michael Y.; Grove, Megan L.; Hopkins, Paul N.; Boerwinkle, Eric; Borecki, Ingrid B.; Ordovas, Jose M.; Levy, Daniel; Tiwari, Hemant K.; Absher, Devin M.; Arnett, Donna K.
• Is Part Of: Obesity. Volume 23:Number 7(2015:Jul.)
• Page Start: 1493
• Page End: 1501
• Publication Date: 2015-07
• Subjects: Obesity -- Periodicals; 616.398005
• DOI: 10.1002/oby.21111
• Languages: English
• ISSNs: 1930-7381

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="oby21111-sec-0001" sec-type="section"> <title>Objective</title> <p>To conduct an epigenome‐wide analysis of DNA methylation and obesity traits.</p> </sec> <sec id="oby21111-sec-0002" sec-type="section"> <title>Methods</title> <p>DNA methylation was quantified in CD4+ T‐cells using the Illumina Infinium HumanMethylation450 array in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. Methylation at individual cytosine‐phosphate‐guanine (CpG) sites as a function of body mass index (BMI) and waist circumference (WC), adjusting for age, gender, study site, T‐cell purity, smoking, and family structure, was modeled.</p> </sec> <sec id="oby21111-sec-0003" sec-type="section"> <title>Results</title> <p>Epigenome‐wide significant associations between eight CpG sites and BMI and five CpG sites and WC, successfully replicating the top hits in whole blood samples from the Framingham Heart Study (<italic>n</italic> = 2, 377) and the Atherosclerosis Risk in Communities study (<italic>n</italic> = 2, 097), were found. Top findings were in <italic>CPT1A</italic> (meta‐analysis <italic>P</italic> = 2.7 × 10<sup>−43</sup> for BMI and 9.9 × 10<sup>−23</sup> for WC), <italic>PHGDH</italic> (meta‐analysis <italic>P</italic> = 2.0 × 10<sup>−15</sup> for BMI and 4.0 × 10<sup>−9</sup> for WC), <italic>CD38</italic> (meta‐analysis <italic>P</italic> = 6.3 × 10<sup>−11</sup> for BMI and 1.6 × 10<sup>−12</sup> for WC), and long intergenic non‐coding RNA 00263 (meta‐analysis <italic>P</italic> = 2.2 × 10<sup>−16</sup> for BMI and 8.9 × 10<sup>−14</sup> for WC), regions with biologically plausible relationships to adiposity.</p> </sec> <sec id="oby21111-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>