Metabolic Syndrome (MetS) is a cluster of conditions that can increase the risk of chronic diseases like, type 2 diabetes. Multiple reports show alterations in DNA methylation patterns are associated with the condition. Using cross-sectional data from Hypertension Genetic Epidemiology Network (HyperGEN) (N=614 African Americans (AA)) and Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) (N=995 European Americans (EA)), we created a risk score model for MetS. First, we selected specific cytosine-guanine dinucleotides (CpG) sites measured on Illumina Methyl450 arrays previously found to be significantly associated to MetS (CPT1A cg00574958, PHOSPHO1 cg02650017, ABCG1 cg06500161, SREBF1 cg11024682, SOCS3 cg18181703, TXNIP cg19693031). Using the HyperGEN parameter estimates for the single CpGs as weights, we calculated a methylation risk score in HyperGEN which was validated in GOLDN. We then conducted an association analysis using a generalized linear mixed model to test the association between the methylation risk score (MetS-score) and MetS, adjusting for age, sex, study site, 4 ancestry principal components, and family structure. In HyperGEN we performed a 100,000-permutation test to determine statistical significance of the score with MetS. Results showed the risk score was significantly associated with MetS in both populations (HyperGEN p=6.36x-10; GOLDN p=2x-16), with a 1 standard deviation increase in the score being associated with 2.25 (95% CI, 1.79 - 2.86) higher odds of having MetS in HyperGEN and a 2.45 (CI 95%, 2.02 - 3.00) higher odds of having MetS in GOLDN. Lastly, we compared the model fitness of the GOLDN MetS model with and without the MetS-score. AIC criterion suggested the model including the score was a better fit (no score = 1173.99; with score = 1112.61).
In conclusion, we created a methylation risk score strongly associated with MetS which should be further investigated for its ability to predict MetS risk in both AAs and EAs.
B.A. Minniefield: None. M. Irvin: None. B. Hidalgo: None. H.K. Tiwari: None. A. Patki: None. N. Chaudhary: None.
National Heart, Lung, and Blood Institute (3R01HL123782-02S1)