In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10−7 was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6x10-14 and P for cg17058475 = 1.2x10-9). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future.
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The GOLDN study (DKA) was funded by the US National Institutes of Health (NIH)/National Heart, Lung and Blood Institutes (http://www.nhlbi.nih.gov) grants R01HL104135 and U01HL72524. The Bogalusa Heart Study (GSB) was supported by grants R01AG016592 from the National Institute on Aging (https://www.nia.nih.gov) and R01ES021724 from National Institute of Environmental Health Science (http://www.niehs.nih.gov).
Data are available from dbGaP (http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000741.v1.p1).
Das, Mithun; Sha, Jin; Hidalgo, Bertha; Aslibekyan, Stella; Do, Anh N.; Zhi, Degui; Sun, Dianjianyi; Zhang, Tao; Li, Shengxu; Chen, Wei; Srinivasan, Sathanur R.; Tiwari, Hemant K.; Absher, Devin; Ordovas, Jose M.; Berenson, Gerald S.; Arnett, Donna K.; and Irvin, Marguerite R., "Association of DNA Methylation at CPT1A Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study" (2016). Epidemiology Faculty Publications. 17.