Table 2.
Hazard ratios (95 % CIs) of the common differentially methylated positions for cardiovascular disease incidence and mortality comparing the 90th vs the 10th percentile of methylation obtained from the Cox Iterative Sure Independence Screening model coupled with adaptive elastic-net.
| CpG | Chr | Gene | Function | Location | CVD incidence |
CVD mortality |
|---|---|---|---|---|---|---|
| HR (95 % CI) | HR (95 % CI) | |||||
| cg13251119 | 1 | EPS8L3 | Unknown function | Body | 0.51 (0.29, 1.00) | 0.18 (0.06, 0.63) |
| cg00841849 | 2 | ID2 | Cellular growth, senescence, differentiation, apoptosis, angiogenesis, neoplastic transformation |
Intergenic | 0.57 (0.40, 0.84) | 0.63 (0.32, 1.01) |
| cg14066163 | 17 | Unknown | - | Intergenic | 0.63 (0.39, 1.00) | 0.67 (0.31, 1.17) |
| cg25371036 | 11 | AMOTL1 | Endothelial cell migration, capillary formation | TSS1500 | 0.71 (0.54, 0.92) | 0.42 (0.27, 0.73) |
| cg03362418 | 22 | TYMP | Angiogenesis and endothelial cell growth. Proposed as therapeutic target for CVD | Body | 0.73 (0.50, 1.02) | 0.51 (0.29, 0.94) |
| cg25452273 | 15 | PPCDC | Biosynthesis of coenzyme A. Metabolism of water-soluble vitamins | Body | 1.25 (0.96, 1.81) | 1.80 (1.00, 3.42) |
| cg18130370 | 22 | NCF4 | Arterial remodeling and advanced atherosclerosis | Body | 0.79 (0.48, 1.12) | 0.44 (0.19, 0.99) |
| cg00451635 | 16 | EMP2 | Blood vessel endothelial cell migration and angiogenesis | TSS1500 | 1.11 (0.86, 1.33) | 0.68 (0.46, 1.00) |
| cg06970472 | 4 | APBB2 | Beta cell function, insulin secretion impairment in mice | Body | 1.22 (0.93, 1.61) | 0.69 (0.43, 1.05) |
Hazard ratios are from an adaptive elastic-net model fitted on the selected CpG sites by ISIS – Aenet. 95 % confidence intervals were calculated using quantile bootstrap.
Models were adjusted for age, sex, smoking status (never, former, current), BMI, LDL cholesterol, HDL cholesterol, hypertension (yes/no), diabetes status (yes/no), systolic blood pressure, albuminuria (micro, macro, normal), study center (Arizona, Oklahoma, North Dakota and South Dakota), cell counts (CD8T, CD4T, NK, B cells and monocytes) and five genetic PCs.