Table 3.
Genome-wide scan of DNA methylation for an association with fasting level of HOMA-IR (as a continuous variable)
| Chr | CpG site§ | Position | Discovery | Validation | Meta-analysis | CpG context | Gene | Gene region | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Effect† (95% CI) | Effect (95% CI) | p | Effect (95% CI) | p | pQ¥ | ||||||
| chr1 | cg05399785 | 3,564,031 | 3.32 (2.22, 4.43) | 1.20 (− 3.08, 5.48) | 0.578 | 3.19 (2.12, 4.25) | 4.70E-09 | 0.339 | N Shelf | WDR8 | Body |
| chr1 | cg09823288 | 239,552,128 | − 1.52 (− 2.02, − 1.02) | − 3.51 (− 5.47, -1.56) | 0.001 | − 1.64 (− 2.13, − 1.16) | 1.93E− 11 | 0.050 | S Shore | Intergenic | |
| chr1 | cg11832534 | 3,563,998 | 3.84 (2.47, 5.21) | 2.30 (− 2.18, 6.78) | 0.311 | 3.70 (2.40, 5.01) | 2.67E-08 | 0.513 | N Shelf | WDR8 | Body |
| chr1 | cg14476101 | 120,255,992 | − 1.77 (− 2.25, − 1.30) | − 3.73 (− 5.65, − 1.80) | 0.0002 | − 1.89 (− 2.35, − 1.43) | 1.08E-15 | 0.050 | S Shore | PHGDH | Body |
| chr1 | cg16246545 | 120,255,941 | − 1.91 (− 2.54, − 1.28) | − 3.01 (− 5.39, − 0.63) | 0.014 | − 1.99 (− 2.60, − 1.38) | 1.77E-10 | 0.374 | S Shore | PHGDH | Body |
| chr1 | cg16395997 | 3,562,798 | 2.18 (1.39, 2.96) | 2.45 (− 0.54, 5.44) | 0.107 | 2.19 (1.43, 2.95) | 1.60E-08 | 0.860 | S Shore | WDR8 | Body |
| chr1 | cg17901584* | 55,353,706 | − 2.22 (− 2.94, − 1.49) | − 3.01 (− 5.66, − 0.36) | 0.027 | − 2.27 (− 2.97, − 1.58) | 1.85E-10 | 0.568 | S Shore | DHCR24 | TSS1500 |
| chr1 | cg19693031 | 145,441,552 | − 2.66 (-3.26, − 2.07) | − 4.49 (− 6.37, − 2.62) | < 0.001 | − 2.83 (− 3.40, − 2.27) | 9.98E-23 | 0.065 | OpenSea | TXNIP | 3'UTR |
| chr2 | cg00391067 | 39,145,400 | 2.93 (1.86, 4.01) | 4.25 (0.07, 8.43) | 0.046 | 3.02 (1.98, 4.05) | 1.20E-08 | 0.544 | OpenSea | LOC100271715 | TSS1500 |
| chr3 | cg27275941** | 15,751,015 | − 2.10 (− 2.89, − 1.31) | − 0.55 (− 3.60, 2.50) | 0.721 | − 2.00 (− 2.77, − 1.24) | 2.77E-07 | 0.327 | OpenSea | ANKRD28 | Body |
| chr4 | cg06690548 | 139,162,808 | − 1.80 (− 2.40, − 1.20) | − 4.25 (− 6.83, − 1.66) | 0.002 | − 1.93 (− 2.51, − 1.34) | 8.51E-11 | 0.067 | OpenSea | SLC7A11 | Body |
| chr5 | cg26403843 | 158,634,085 | 1.70 (1.06, 2.34) | 1.03 (− 0.76, 2.81) | 0.257 | 1.62 (1.02, 2.22) | 1.34E-07 | 0.482 | N Shelf | RNF145 | Body |
| chr6 | cg13123009 | 31,681,882 | 3.34 (2.16, 4.52) | 2.74 (− 0.30, 5.79) | 0.077 | 3.26 (2.16, 4.36) | 6.17E-09 | 0.718 | OpenSea | LY6G6E | TSS200 |
| chr6 | cg17501210 | 166,970,252 | − 1.86 (-2.49, − 1.23) | − 5.21 (− 8.07, -2.36) | 0.0005 | − 2.02 (− 2.64, − 1.41) | 1.18E-10 | 0.023 | OpenSea | RPS6KA2 | Body |
| chr7 | cg01676795** | 75,586,348 | 1.92 (1.19, 2.65) | 0.96 (− 2.66, 4.59) | 0.599 | 1.88 (1.16, 2.60) | 2.59E-07 | 0.608 | OpenSea | POR | Body |
| chr7 | cg19390658* | 30,636,176 | − 1.53 (-2.07, − 1.00) | − 1.29 (− 3.04, 0.46) | 0.146 | − 1.51 (− 2.02, − 1.00) | 6.86E-09 | 0.792 | S Shore | GARS | Body |
| chr7 | cg21429551* | 30,635,762 | − 1.28 (− 1.76, -0.80) | − 1.43 (− 2.94, 0.09) | 0.065 | − 1.29 (− 1.75, − 0.84) | 2.29E-08 | 0.855 | S Shore | GARS | Body |
| chr8 | cg20907614** | 29,914,963 | − 1.97 (-2.72, − 1.22) | − 0.73 (− 3.53, 2.06) | 0.602 | − 1.88 (− 2.60, -1.16) | 3.35E-07 | 0.397 | OpenSea | Intergenic | |
| chr10 | cg01391548** | 97,068,696 | − 2.18 (− 2.99, − 1.37) | − 2.73 (− 4.79, − 0.67) | 0.010 | − 2.25 (− 3.01, − 1.50) | 4.43E-09 | 0.623 | OpenSea | Intergenic | |
| chr10 | cg02556345 | 124,181,965 | − 2.78 (-3.83, − 1.72) | − 2.20 (− 5.91, 1.50) | 0.241 | − 2.73 (− 3.74, -1.72) | 1.22E-07 | 0.767 | OpenSea | PLEKHA1 | Body |
| chr10 | cg08284263** | 92,958,627 | − 3.57 (− 4.90, − 2.24) | − 1.77 (− 5.73, 2.19) | 0.376 | − 3.38 (− 4.64, − 2.12) | 1.46E-07 | 0.392 | OpenSea | Intergenic | |
| chr10 | cg08994060 | 6,214,026 | − 2.02 (− 2.78, − 1.27) | − 3.25 (− 6.05, − 0.46) | 0.023 | − 2.11 (− 2.83, − 1.38) | 1.35E-08 | 0.398 | OpenSea | PFKFB3 | Body |
| chr10 | cg26262157 | 6,214,079 | − 2.13 (− 2.92, − 1.34) | − 3.45 (− 6.11, − 0.79) | 0.012 | − 2.24 (− 2.99, − 1.48) | 5.89E-09 | 0.344 | OpenSea | PFKFB3 | Body |
| chr11 | cg00574958 | 68,607,622 | − 9.68 (− 11.83, − 7.53) | − 8.83 (− 13.70, − 3.96) | 0.001 | − 9.54 (− 11.50, − 7.58) | 1.65E− 21 | 0.751 | N Shore | CPT1A | 5'UTR |
| chr11 | cg17058475 | 68,607,737 | − 4.52 (− 6.06, − 2.98) | − 5.53 (− 9.14, − 1.91) | 0.003 | − 4.67 (− 6.09, − 3.26) | 8.84E− 11 | 0.610 | N Shore | CPT1A | 5'UTR |
| chr13 | cg19750657 | 38,935,967 | 2.62 (1.84, 3.40) | 2.32 (-1.02, 5.67) | 0.171 | 2.60 (1.85, 3.36) | 1.71E-11 | 0.863 | OpenSea | UFM1 | 3'UTR |
| chr15 | Cg06192883** | 52,554,171 | 3.39 (2.41, 4.37) | 3.94 (1.08, 6.80) | 0.008 | 3.45 (2.53, 4.37) | 2.31E-13 | 0.718 | OpenSea | MYO5C | Body |
| chr16 | cg26663590 | 28,959,310 | 2.27 (1.44, 3.09) | 3.59 (0.24, 6.95) | 0.036 | 2.35 (1.55, 3.15) | 9.35E-09 | 0.446 | S Shore | Intergenic | |
| chr17 | cg13274938 | 38,493,822 | 3.22 (2.07, 4.36) | 3.78 (-0.85, 8.41) | 0.109 | 3.25 (2.14, 4.36) | 9.39E-09 | 0.815 | N Shelf | RARA | Body |
| chr17 | cg18772573 | 71,257,980 | 2.64 (1.63, 3.65) | 3.13 (-1.69, 7.95) | 0.201 | 2.66 (1.67, 3.65) | 1.35E-07 | 0.845 | OpenSea | CPSF4L | 1stExon |
| chr17 | cg24366564** | 2,843,149 | 2.84 (1.74, 3.93) | -0.91 (-4.26, 2.44) | 0.589 | 2.47 (1.43, 3.50) | 3.26E-06 | 0.035 | OpenSea | RAP1GAP2 | Body |
| chr21 | cg06500161** | 43,656,587 | 3.75 (2.86, 4.65) | 7.01 (3.66, 10.36) | < 0.001 | 3.97 (3.11, 4.83) | 1.32E-19 | 0.062 | S Shore | ABCG1 | Body |
| chr21 | cg08309687£ | 35,320,596 | -2.10 (-2.70, -1.49) | -3.34 (-6.17, -0.51) | 0.021 | -2.15 (-2.74, -1.56) | 7.59E-13 | 0.392 | OpenSea | Intergenic | |
| chr21 | cg27243685** | 43,642,366 | 3.71 (2.45, 4.97) | 10.83 (4.64, 17.02) | 0.001 | 4.00 (2.77, 5.24) | 2.13E-10 | 0.025 | S Shelf | ABCG1 | Body |
| chr22 | cg09349128 | 50,327,986 | -3.15 (-4.30, -2.01) | -3.71 (-6.95, -0.46) | 0.026 | -3.22 (-4.30, -2.14) | 5.31E-09 | 0.749 | N Shore | Intergenic | |
Chr chromosome, CI Confidence interval, CpG CpG dinucleotide, Effect Effect size; HOMA-IR, homeostatic model assessment–insulin resistance; TSS200, 0–200 bp upstream of transcription start site; TSS1500, 200–1500 bp upstream of transcription start site; UTR, untranslated region. Numbers in bold face are statistically significant
§ Annotation used R v.0.6.0.IlluminaHumanMethylation450kanno.ilmn12.hg19: Annotation for Illumina's 450 k methylation arrays
† Each effect size of the CpGs in the discovery stage was at the epigenome-wide significance level (p < 1E-007)
a Effect size adjusted by age and leukocyte heterogeneities (CD8+CD28−CD45RA− T cell, naïve CD8 T cell, plasma blast, CD4+ T cell, natural killer cell, monocyte, and granulocyte)
¥ p value for Cochran’s Q
* Promoter associated
** Enhancer associated
£ Enhancer and promoter associated