Table 2.
Differentially methylated CpGs from the three meta-analysis models and associations from prospective analyses, CRIC study and eFORGE-TF database
| CpG Site | Gene | Minimal model (p) | Minimal + Smoking model (p) | Maximal model (p) | Progression to kidney failure (p) | DKD CRIC cohort (p) | eFORGE-TF (p) |
|---|---|---|---|---|---|---|---|
| cg19693031 | TXNIP | 6.75 × 10−7 | 8.80 × 10−8 | 6.17 × 10−7 | 6.22 × 10−14 (HbA1c) | ||
| cg05284887 | GJA5 | 3.35 × 10−9 | 2.60 × 10−7 | 1.42 × 10−5 | 3.93 × 10−5 | ||
| cg21961721 | SLC27A3 | 2.34 × 10−14 | 5.57 × 10−11 | 2.75 × 10−10 | 1.72 × 10−4 | <2.2 × 10−308 (eGFR) | |
| cg08150816 | NME7 | 8.23 × 10−15 | 3.71 × 10−13 | 4.62 × 10−10 | 7.16 × 10−5 | ||
| cg01895164 | PAFAH2, EXTL1 | 9.06 × 10−12 | 1.79 × 10−8 | 7.79 × 10−6 | 1.08 × 10−6 | ||
| cg23527387 | REV1 | 4.12 × 10−11 | 2.80 × 10−8 | 2.26 × 10−3 | 5.19 × 10−3 | ||
| cg02841972 | GRHL1, KLF11 | 1.35 × 10−8 | 4.65 × 10−8 | 1.53 × 10−6 | |||
| cg05710777 | LINC01800 | 2.95 × 10−18 | 4.05 × 10−15 | 1.98 × 10−11 | 9.78 × 10−4 | 3.58 × 10−6 | |
| cg12864625 | MBNL1 | 1.16 × 10−10 | 1.62 × 10−7 | 9.98 × 10−6 | |||
| cg18376497 | INPP4B | 1.78 × 10−10 | 3.15 × 10−9 | 1.56 × 10−6 | 3.81 × 10−4 | 0.005 (eGFR) | |
| cg05165263 | IRF2 | 9.87 × 10−8 | 3.64 × 10−6 | 8.18 × 10−5 | 1.04 × 10−3 | 6.62 × 10−5 (eGFR) | 5.42 × 10−6 |
| cg12378834 | C5orf66 | 4.04 × 10−10 | 3.06 × 10−7 | 2.43 × 10−4 | |||
| cg11414254 | ZNF346, UIMC1 | 4.02 × 10−8 | 2.34 × 10−6 | 3.63 × 10−4 | |||
| cg19996939 | HBS1L, MYB | 3.40 × 10−8 | 2.16 × 10−8 | 2.84 × 10−6 | 2.91 × 10−6 | ||
| cg02917536 | TAB2 | 9.28 × 10−8 | 9.77 × 10−7 | 2.73 × 10−4 | 0.018 (eGFR) | ||
| cg03546163 | FKBP5 | 3.63 × 10−13 | 8.90 × 10−10 | 1.77 × 10−4 | 0.003 (HbA1c) | ||
| cg00008629 | PTBP3 | 5.41 × 10−15 | 1.17 × 10−12 | 2.90 × 10−9 | |||
| cg15167811 | PTBP3 | 3.03 × 10−11 | 2.93 × 10−9 | 6.84 × 10−7 | |||
| cg13125822 | GRK5 | 4.93 × 10−10 | 1.64 × 10−8 | 1.89 × 10−6 | |||
| cg03026982 | NAV2 | 1.43 × 10−9 | 3.20 × 10−7 | 5.30 × 10−5 | |||
| cg10473623 | NAV2 | 1.63 × 10−8 | 1.85 × 10−6 | 2.31 × 10−4 | |||
| cg05325763 | CPT1A | 2.08 × 10−11 | 4.83 × 10−9 | 1.93 × 10−7 | |||
| cg17058475 | CPT1A | 5.90 × 10−8 | 1.07 × 10−6 | 2.68 × 10−5 | 0.009 (ALB) | 9.52 × 10−6 | |
| cg08230697 | STAB2 | 1.82 × 10−8 | 1.23 × 10−6 | 5.19 × 10−5 | |||
| cg10072464 | ADPRHL1 | 9.09 × 10−10 | 3.02 × 10−7 | 4.96 × 10−7 | 1.04 × 10−3 | 0.002 (eGFR) | 2.44 × 10−7 |
| cg24382141 | PSKH1 | 3.44 × 10−8 | 1.01 × 10−5 | 1.46 × 10−3 | 0.002 (eGFR) | ||
| cg22815707 | ANKRD12 | 1.16 × 10−9 | 1.70 × 10−8 | 4.82 × 10−6 | 6.31 × 10−6 | ||
| cg25544931 | ZNF763, ZNF433-AS1 | 2.58 × 10−27 | 1.85 × 10−21 | 7.90 × 10−19 | 4.01 × 10−6 | 2.09 × 10−5 (eGFR) | |
| cg17944885 | ZNF788P, ZNF625-ZNF20 | 1.97 × 10−44 | 1.38 × 10−36 | 8.91 × 10−27 | 1.40 × 10−21 | 3.72 × 10−13 (eGFR) | |
| cg06587767 | PIP5K1C | 2.08 × 10−9 | 9.47 × 10−7 | 2.98 × 10−4 | |||
| cg02711608 | SLC1A5 | 8.89 × 10−12 | 2.62 × 10−9 | 4.77 × 10−8 | |||
| cg12230203 | PTGIS, B4GALT5 | 7.79 × 10−8 | 1.25 × 10−6 | 5.20 × 10−6 | 6.63 × 10−6 |
The CpG methylations included met the EWAS significance threshold (corrected p ≤ 9.9 × 10−8) in one of the three meta-analysis adjustment models. P-values in the meta-analysis were derived from hierarchal linear models including the covariates age, sex and six WCCs (minimal model), or age, sex, six WCCs and current smoking status (Minimal + smoking model) or age, sex, six WCCs, current smoking status, HbA1c, HDL cholesterol, triglycerides, duration of diabetes and body mass index (Maximal model). For intergenic CpGs, the two closest downstream and upstream genes are given. Empty cells did not have supporting evidence (p < 1 × 10−5) for transcription factors using eFORGE-TF. Empty cells also indicate that no evidence achieved at least p ≤ 0.05 from the CRIC database lookup. The phenotype with lowest p-value shown for the CRIC cohort, which include individuals with any type of diabetes.
Abbreviations
CRIC Chronic Renal Insufficiency Cohort Study, eGFR estimated glomerular filtration rate, ALB Albuminuria, HbA1c Haemoglobin A1c, T2D type 2 diabetes, TF transcription factor.