Table 2.
Methylation Studies in blood.
| Research Article | Study Information | Cohorts—c/c | Gene (CG Site) | Position | T2D Risk/Main Findings | |
|---|---|---|---|---|---|---|
| Chambers et al. (2015) [117] | a Nested case-control study EWAS (methylation bead chip); b Replication testing candidate (bisulfite pyrosequencing) | a Indian Asians from the LOLIPOP study, (1074/1590); b Europeans from the LOLIPOP study, KORA S3, and KORA S4 studies [306/6760] § | ABCG1 (cg0650016) | Body | RR (95%CI) | 1.09 (1.07–1.11) |
| PHOSPHO1 (cg02650017) | Body | 0.94 (0.92–0.95) | ||||
| SOCS3 (cg18181703) | Body | 0.94 (0.92–0.96) | ||||
| SREBF1 (cg11024682) | Body | 1.07 (1.04–1.09) | ||||
| TXNIP (cg19693031) | 3′-UTR | 0.92 (0.90–0.94) | ||||
| Kulkarni et al. (2015) [118] | Family-based study EWAS (methylation bead chip) | Mexican-American from the San Antonio Family Heart Study [850 (~21% T2D)] | ABCG1 (cg06500161) | Body | Association between T2D status and methylation levels | |
| TXNIP (cg19693031) | 3′-UTR | |||||
| SAMD12 (cg01192487) | 5′-UTR | |||||
| Dayeh et al. (2016) [96] | Replication testing candidate (bisulfite pyrosequencing) | Europeans from the Botnia prospective study (129/129) § | ABCG1 (cg0650016) | Body | RR (95%CI) | 1.09 (1.02–1.16) |
| PHOSPHO1 (cg02650017) | Body | 0.85 (0.75–0.95) | ||||
| Walaszczyk et al. (2017) [119] | Replication testing EWAS (methylation bead chip) | Europeans from the Lifelines study (100/98) | ABCG1 (cg06500161) | Body | Association between T2D status and methylation levels | |
| SREBF1 (cg11024682) | Body | |||||
| TXNIP (cg19693031) | 3′-UTR | |||||
| LOXL2 (cg24531955) | 3′-UTR | |||||
| SLC1A5 (cg02711608) | 1st Exon | |||||
| Karaglani et al. (2018) [123] | Case-control study (MeDIP on candidate genomic regions) | a Europeans with T2D under sulfonylureas treatment who experienced hypoglycemic events (88/83) | ABCC8 (/) | Promoter | Association of DNA methylation at ABCC8 promoter to non-hypoglycemic events in sulfonylureas-treated T2D patients | |
| KCNJ11 (/) | Promoter | |||||
| Cardona et al. (2019) [120] | a Nested case-control study EWAS (methylation bead chip); b Replication testing EWAS (methylation bead chip) | a Europeans from the EPIC-NORFOLK study (563/701) b Indian Asians from the LOLIPOP study (1074/1590) b Americans from the FHS study (403/2204) | ABCG1 (cg06500161) | Body | RR (95%CI) | 1.65 (1.45–1.89) |
| SREBF1 (cg11024682) | Body | 1.56 (1.35–1.79) | ||||
| TXNIP (cg19693031) | 3′-UTR | 0.52 (0.46–0.6) | ||||
| CPT1A (cg00574958) | 5′-UTR | 0.69 (0.61–0.78) | ||||
| Krause et al. (2019) [121] | Replication testing candidate (bisulfite pyrosequencing) |
Europeans from the Northern Germans cohorts, Cohort 1 (176 control) Cohort 2 (100 obese) |
ABCG1 (cg06500161) | Body | Risk group stratification based on the combined methylation scores | |
| SREBF1 (cg11024682) | Body | |||||
| García-Calzón et al. (2020) [122] Part 1 |
a Case-control study EWAS on the Discovery cohort (methylation bead chip) b Case-control study EWAS on the replication cohorts (methylation bead chip) |
a Europeans from the ANDIS study, responders/non-responders to metformin (26/21) b Europeans from the ANDIS study, responders/non-responders to metformin (48/39) b Europeans from the AN-DiU and OPTIMED cohorts, responders/non-responders to metformin (47/31) |
/ (cg00153082) | Intergenic | Stratification of glycemic responders and non-responders to metformin therapy based on the combined methylation risk scores of the 11 CpG sites | |
| CFAP58 (cg03529510) | Body | |||||
| OR4S1 (cg05402062) | TSS1500 | |||||
| GPHA2 (cg16704073) | Body | |||||
| / (cg01894192) | Intergenic | |||||
| SAP130 (cg16240962) | TSS1500 | |||||
| SEPT11 (cg01070242) | 5′-UTR/Body | |||||
| / (cg08713722) | Intergenic | |||||
| LRRN2 (cg05151280) | 5′-UTR | |||||
| CST1 (cg07511259) | TSS1500 | |||||
| / (cg01282725) | Intergenic | |||||
| García-Calzón et al. (2020) [122] Part 2 |
a Case-control study EWAS on the Discovery cohort (methylation bead chip) b Case-control study EWAS on the replication cohorts (methylation bead chip) |
a Europeans from the ANDIS study, tolerant/intolerant to metformin (66/17) b Europeans from the ANDIS study, tolerant/intolerant to metformin (37/11) b Europeans from the AN-DiU and the OPTIMED cohorts, tolerant/intolerant to metformin (15/5) |
SCYL1 (cg27553780) | Body | Stratification of tolerant and intolerant individuals to metformin therapy based on the combined methylation risk scores of the 4 CpG sites | |
| FOXA2 (cg12356107) | TSS1500 | |||||
| PGM1 (cg02994863) | 1st Exon | |||||
| FAM107A (cg08148545) | TSS200/Body | |||||
| Juvinao-Quintero et al. (2021) [124] | Meta EWAS EWAS (methylation bead chip) |
Europeans from the ALSPAC, LBC1936, RSIII-1 and RS-Bios studies (340/3088) | ABCG1 (cg06500161) | Body | RR (95% CI) | 1.13 (1.06–1.21) |
| TXNIP (cg19693031) | 3′UTR | 0.93 (0.89–0.98) | ||||
| CPT1A (cg00574958) | 5′-UTR | 0.79 (0.62–1.00) | ||||
| HDAC4 (cg00144180) | 5′-UTR | 1.08 (1.01–1.16) | ||||
| SYNM (cg16765088) | Intergenic | 0.93 (0.88–0.99) | ||||
| miR23a (cg24704287) | Intergenic | 0.95 (0.89–1.02) | ||||
Abbreviations: a, phase 1 of the study design; b, phase 2 of the study design; RR, relative risk; 95% CI, 95% confidence interval; LOLIPOP study, London Life Sciences Prospective Population Study; KORA S3 and 4: Kooperative Gesundheitsforschung in der Region Augsburg Study 3 and Study 4; EPIC-Norfolk study, European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study; FHS, Framingham Heart Study; ANDIS, All New Diabetics In Scania study; AN-DiU, All New Diabetics in Uppsala County; OPTIMED, Optimized program of personalized treatment of type 2 diabetes; ALSPAC, the Avon Longitudinal Study of Parents and Children; LBC1936, the Lothian Birth Cohort of 1936; RSIII-1 and RS-Bios, the Rotterdam Study III-1 and the Rotterdam Study-Biobank-Based Integrative Omics Studies. § Prospective cohort study: participants were non-diabetic at baseline and developed diabetes during follow-up (or not). Samples were investigated at the baseline.