Table 4.
EWASs on kidney disease and related traits in individuals with diabetes.
| Study | Ethnicity | Tissue | Phenotype | Cases | Controls | N Total | CpGs (array) | p-threshold | N significant CpGs |
|---|---|---|---|---|---|---|---|---|---|
| Bell, 2010 (120) | White European | Blood | DKD | 96 (T1D: 100%) | 96 (T1D: 100%) |
192 | 27,578 (27K) | PFDR < 0.05 | 19 (PFDR < 0.05); none with PFDR <10−8 |
| Sapienza, 2010 (121) | African American/Hispanic | Saliva | DKD | 24 (T2D: 87%, T1D: 13%) | 24 (T2D: 100%) |
48 | 27,578 (27K) | Diffscore** > 20 or < −20 | 2,870, of which 30 remained significant after FDR adjustment (PFDR < 0.05) |
| Smyth, 2014 (122) | White European | Blood | CKD/DKD | 255 (T1D: 44%) | 152 (T1D: 74%) |
407 | 485,577 (450K) | PFDR < 10−8 | 52 CpGs (PFDR < 10−8) in 23 genes |
| Swan, 2015 (123) | White European | Blood | DKD | 196 (T1D: 100%) | 246 (T1D: 100%) |
442 | 450* (27k, 450K) |
PFDR < 10−8 | 54 (PFDR < 10−8) |
| Qiu, 2018 (124) | American PIMA Indians | Blood | eGFR; ESKD; eGFR slope | 80 (T2D: 100%) | 101 (T2D: 100%) |
181 | 397,063 (450K) | PFDR < 0.05 | eGFR and ESKD: none (PFDR < 0.05); 77 (eGFR slope, PFDR < 0.05) |
| Gluck, 2019 (125) | Mixed | Kidney tubules | degree of kidney fibrosis | 91 (22 with DKD) | 0 | 91 | 321,473 (450 K) | PFDR < 0.05 | Degree of fibrosis: 203 (PFDR < 0.05) of which 65 replicated (p < 0.05) |
| Sheng, 2020 (126) | Mixed | Blood | eGFR, eGFR slope, albuminuria | 473 (all with diabetes) | 0 | 473 | 866,836 (EPIC) | P < 5 × 10−5 (discovery), p < 6.4 × 10−8 (Bonferroni) | Albuminuria: 73 (P < 5 × 10−5), eGFR: 99 (P < 5 × 10−5); 1 (6.4 × 10−8), eGFR slope: 111 (P < 5 × 10−5); 3 (6.4 × 10−8) |
| Smyth, 2020 (127) | White European | Blood | DKD | 150 (T1D: 100%) | 100 (T1D: 100%) |
677 | 482,421 (450K) | PFDR < 10−8, Δβ > 0.2 | 22 |
| Kim, 2021 (128) | East Asian | Blood | DKD | 87 (T2D: 100%) | 80 (T2D: 100%) | 167 | 749 315 (EPIC) | PFDR < 9.0 × 10–8 | 3 (PFDR < 9.0 × 10–8) |
| Smyth, 2021 (129) | White European | Blood | ESKD (4 analysis models) | 107 (T1D: 100%) | 253 (T1D: 100%) | 360 | 862,927 (EPIC) |
PFDR
< 10−8, FC ± 2 |
36 (PFDR < 10−8, FC ± 2 across all four models) |
| Lecamwasam, 2021 (130) | Mixed | Blood | late CKD (eGFR<45) vs. early (eGFR≥45) | 38 (T1D: 8%, T2D: 87%) |
83 (T1D: 20%, T2D: 80%) | 119 | 764 333 (EPIC) | PFDR < 0.05 | 1 (PFDR < 0.05) |
| Smyth, 2022 (77) | White European | blood | DKD (3 analysis models) | 651 (T1D:100%) | 653 (T1D: 100%) | 1304 | 763 064 (EPIC) | PFDR <9 × 10−8 | 32 (PFDR < 9 × 10−8) |
27K, Illumina Infinium HumanMethylation 27K; 450K, Illumina Infinium HumanMethylation 450K; EPIC, Illumina Infinium HumanMethylation EPIC v1.
*Only CpGs within mitochondrial genes were surveyed.
**Diffscore = 10sgn(b-valueESRD − b-valuediabetes no nephropathy) log10p.