Abstract
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.
Highlights
Metabolic syndrome (MetS) is a constellation of interrelated risk factors of metabolic origin [1]
We present a DNA methylation epigenome-wide association study (EWAS) of MetS in subjects of European descent from the Genetics of Lipid Lowering Drugs and Diet Network Study (GOLDN)
We observed lower methylation at cg00574958 was significantly associated with meeting waist circumference (WC), TG, Blood pressure (BP), and fasting blood glucose (FBG) criteria for MetS with P < 0.001 and the high density lipoprotein cholesterol (HDLc) criterion with P < 0.01
Summary
Metabolic syndrome (MetS) is a constellation of interrelated risk factors of metabolic origin [1]. Persons with MetS are at twice the risk for cardiovascular disease (CVD) and have a fivefold risk for type 2 diabetes (T2D) [2] Both genetic and environmental factors play a role in the pathogenesis of MetS. We present a DNA methylation epigenome-wide association study (EWAS) of MetS in subjects of European descent from the Genetics of Lipid Lowering Drugs and Diet Network Study (GOLDN). The GOLDN study is composed of families of European descent recruited from field centers in Minneapolis, MN and Salt Lake City, UT. It is part of the NHLBI Family Heart Study and has been described in detail in prior publications [8,9,10]. To previous publications in GOLDN, these PCs were used to adjust for T-cell purity in the association analysis [8,9,10]
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