Table 1.
Epigenome-wide DNA methylation association analyses of obesity in different populations
| References | Sample size | Tissue | Phenotype | Gene | CpG number |
|---|---|---|---|---|---|
| Martin et al. [20] | 187 mother-female /173 mother-male offsprings | Cord blood leukocytes |
BMI z-score (BMIz) |
TAPBP (female offspring) | 876; 293 |
| Jönsson et al. [21] | 208 | Cord blood | BMIz | DISC1, GBX2, HERC2, HUWE1 | 379 |
| Huang et al. [22] | 78 | Whole blood | BMIz | FYN, PIWIL4, TAOK3 | 129 differentially methylated CpG |
| Fradin et al. [23] | 40 | Whole blood cells | BMI, BMIz | LMX1A, ACSF3 | 31 CpGs (obesity); 151 (severe obesity, > 10%) |
| Rzehak et al. [24] | 374 | Whole blood | BMI, fat-mass, fat-free-mass, fat-mass-index, fat-free-mass-index | SNED1(IRE-BP1), KLHL6, WDR51A(POC1A), CYTH4-ELFN2, CFLAR, PRDM14, SOS1, ZNF643(ZFP69B), ST6GAL1, C3orf70, CILP2, MLLT4 | BMI (212), fat-mass (230), fat-free-mass (120), fat-mass-index (24), fat-free-mass-index (15) |
| Li et al. [25] | 3 obese cases, 4 controls; 39 obese cases, 42 controls | Peripheral blood leukocytes | BMI | HDAC4, RAX2; SLC25A20; APOA5 and CES1 (negative correlation) | 4 85 000 methylation sites, 226 methylated CpGs |
| Samblas et al. [26] | 24; 91 | White blood cells | BMIz | VIPR2, GRIN2D, ADCYAP1R1, PER3, PTPRS; PTPRS, PER3 with BMI z-score | 734 |
| Huang et al. [27] | 265 | Leukocytes | BMIz | ATOH8, CDC37/MIR1181, COMT/TXNRD2, DDX10, TAS2R40, TBCD | 6 (mid-childhood) |
| He et al. [28] | 263 | Peripheral leukocytes | BMI | SIM1 | 28 |
| Sherwood et al. [29] | 297 | Peripheral blood | BMI trajectories | LEP | 23; cg23381058 (early transient overweight trajectory), cg05091920 (early persistent obesity trajectory) |
| Wang et al. [30] | 325 | Whole blood | BMI status transition | P2RX4, RADIL | 174 |
| Vehmeijer et al. [31] | 4133 children from 23 studies | Cord blood and whole blood | BMI | SFRP5, SLC43A2, SFXN5 | 187 |
| Xu et al. [32] | 48 obese, 48 lean | Peripheral blood samples | BMI | - | 23, 305 |
| Wang et al. [33] | 700, 188, 2097 | Neutrophils, Leukocytes | BMI | HRASLS2, SOCS3, CISH, PIM3, KLF4, HRASLS2 | 76 (novel 29) |
| Wilson et al. [34] | 871 women, 187 women | Blood samples | BMI | ANGPT4, RORC, SOCS3, FSD2, XYLT1, ABCG1, STK39, ASB2, CRHR2 | 4 CpG sites FDR q < 0.05 |
| Kvaløy et al. [35] | 60 lean, 60 obese | Leucocyte | BMI | TEX41, IGHE/IGHG1/IGHD, DMAP1, SETBP1 (novel findings); COX6A1P/FGD2, SBNO2, RPS6KA2, SOCS3 | 10 differentially methylated CpG sites |
| Shen et al. [36] | 927 Mexican American women | Blood DNA samples | BMI, Weight change | HIF3A | 3 (position 46,801,557, 46,801,642, 46,801,699) |
| Guay et al. [37] |
61 30 |
Blood and visceral adipose tissue (VAT) | Waist-to-hip ratio | ADRB3 | - |
| Skuladottir et al. [38] | 16 | Whole blood samples | Weight | SCD1 | 3 (cg00954566, cg24503796, cg14089512) |
| Keller et al. [39] | 120 (90% men) | Blood samples | BMI, Weight-loss | LRRC27, CRISP2, SLFN12, NUDT3, NCOR2 | 15 (negatively correlated with weight change) |
| Ollikainen et al. [40] | 30 twin pairs | Leukocyte DNA | BMI | - | No differentially methylated CpG sites between co-twins discordant for BMI |
| Li et al. [41] | 90, Obesity: 23 pairs of twins (7-16y), including 12 male pairs | Peripheral blood samples | Weight, waist circumference (WC) | cg05684382 (chr: 12) and cg26188191 (chr: 16) | 817471 qualified CpG loci; No positive sites |
| Li et al. [42] | 30 twin pairs (15 male and 15 female pairs) | Whole blood samples | BMI | - | 136; No CpGs reached genome-wide significance |
| Demerath et al. [43] | 2097, 2377, 991, 648 | Leukocyte DNA, Whole-blood DNA | BMI, WC | HIF3A, CPT1A, ABCG1, LGALS3BP, KDM2B, PBX1, BBS2 | Probes: 76 BMI-related, 164 WC-related, 8 BMI change-related |
| Xu et al. [44] | 510 | Whole blood samples | BMI | SOCS3 | 20 (including novel cg18181703) |
| Sun et al. [45] | 995 whites, 490 blacks; 252 whites, 228 blacks; 439 whites, 201 blacks | Whole blood samples | BMI | PROC, PLCH1, SOX2OT, BCL9L, SBNO2, ABCG1 | 349 (266 novel) in whites, 36 (21 novel) in blacks |
| Meeks et al. [46] | 547 | Whole blood samples | BMI, WC | CPT1A, NLRC5, BCAT1 | 18 Differentially methylated positions (DMPs) for BMI and 23 for WC, 14 DMPs overlapped between BMI and WC |
| Giri et al. [47] | 236 | Peripheral blood samples | BMI | BAI3, SLC22A11, ZNF45 | 53; 19 (BAI3), 25 (SLC22A11) and 9 (ZNF45) |
| Dick et al. [48] |
479 339 1789 |
Whole-blood DNA; adipose tissue (n = 635) and skin (n = 395) | BMI | HIF3A | -cg22891070, cg27146050, cg16672562 |
| Sayols-Baixeras et al. [49] |
641 2,515 |
Blood DNA | BMI, WC | Located in 95 loci; INTU, SFRP2, RUNX2, CTTNBP2, CPT1A, CACNA1C, MCF2L, BCL2L2, MPG, KRT16 | 94 (BMI, 70 novel) and 49 (WC, 33 novel) |
| Mendelson et al. [50] | 3,743; replication in 3 external cohorts of 4,055 participants | Whole-blood-derived DNA | BMI | SREBF1 | 83 |
| Dhana et al. [51] |
1,450 2,097 |
Leukocytes | BMI, WC | MSI2, LARS2, BRDT, PSMD1, IFI44L, MAP1A, MAP3K5, LGALS3BP, MAP2K3, DHCR24, CPSF4L, TMEM49 | 14 (BMI) and 26 (WC) |
| Do et al. [52] | 46 studies | Blood-based DNA | BMI, WC | - | 77 (BMI) and 4 (WC) |
| Nikpay et al. [53] | - | Blood-based DNA | BMI | CCNL1, MAST3, SLC5A11, POMC, ADCY3, DNAJC27 | cg21178254, cg02814054, cg06028605, cg01884057 |
| Benton et al. [54] | 15 women | Subcutaneous and omental adipose tissue | BMI | PROX1, PHACTR1, SLC22A8, SMAD3, LCAT, DNM2, LEPR, STAB1, ZNF608, HMGA1, MSRA, TUB, NRXN3, FTO, MC4R | 485,577 |
| Dahlman et al. [55] | 16 women | Abdominal subcutaneous fat cells | BMI | mapped to 3717 unique genes | 8504 |
| Rönn et al. [56] | 23 healthy men | Adipose tissue | BMI | RALBP1, HDAC4, NCOR2, TCF7L2, KCNQ1 | 485,577 probes covering 99% RefSeq genes; 17,975 (7,663 genes) |
| Macartney-Coxson et al. [57] |
681 (subcutaneous) 33 (omental) |
White adipose tissue depots | BMI | PITX2, ISL2, ATP2C2 | 784 and 1129 extended regions |
| Keller et al. [58] |
39 (Men), 66 (women) |
Subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (OVAT) | BMI | HAND2, HOXC6, PPARG, SORBS2, CD36, CLDN1 | 1381 differentially methylated genes (SAT vs OVAT) |
| Crujeiras et al. [59] |
45 (obese) 8–10 (non-obese) |
Subcutaneous adipose tissue and circulating leukocytes | BMI | FGFRL1, NCAPH2, PNKD, SMAD3 | – |
| Turner et al. [60] |
9 (young male) 5 (older adults) |
Skeletal muscle tissue | - | KIF15, DYRK2, FHL2, MRPS33, ABCA17P, HOXD10, HOXD9, HOXD8, HOXA3, HOXC9, HOXB1, HOXB3, HOXC-AS2, HOXC10, HOXC-AS3 | 6–8 |
| Prats-Puig et al. [61] | 16 pregnant women (8 obesity; 8 control) | Umbilical cord tissue | BMI | MYL6, MYH11, TNNT3, TPM2, CXCL2, NCAM1 | 38 |
| Sillanpää et al. [62] |
139 47 |
Blood and muscle tissue |
BMI Body composition |
- | – |
| Day et al. [63] | 7 obese females | Skeletal muscle | BMI | SORBS3 | 30 |
| Nogues et al. [64] | 30 women | Fetal and maternal sides of third-trimester placenta | BMI | LEP, ADPN | – |
| Gagné-Ouellet et al. [65] | 262 mother–offspring | Placental DNA | BMI | TFAP2E, FAM3C, FMN1, MAGI2, SKAP2, BMPR1B | cg22593959 (lower) and cg22436429 (higher) |
| Daniels et al. [66] |
135 Women and Infants (1–2 days) |
Placenta | Weight, weight gain | LEP | – |
| Breton et al. [67] | 276 mother–child dyads | Placenta | BMI | NEGR1 | 30 CpGs; cg26153364, cg23166710, cg04932878, cg1652573, cg23166710 |
| Shrestha et al. [68] | 301 | Placenta | BMI, rate of gestational weight gain | EGFL7, VEZT, MYT1L, DLX5, SLC35F3 | cg14568196, cg15339142, cg02301019 cg17918270, cg20735365, cg17451688, cg1456819 |
| Rounge et al. [69] | 50 lean, 50 heavy adolescent girls | Saliva | BMI | MC2R, IGFBPL1, IP6K1, IGF2BP1 | 100 (7 regions) |
| Oelsner et al. [70] | 92 | Saliva samples | BMI, weight gain | FSTL1, SORCS2, NRF1, DLC1, PPARGC1B, CHN2, NXPH1 | 17 (5 decreased methylation) |
| Dunstan et al. [71] | 431 adolescents aged 10–15 years | Saliva samples | BMIz, WC, and percent body fat | LEP, ICAM-1, CRH, LINE-1 | 3 |
| Kaufman et al. [72] |
321 234 |
Saliva | BMI | PCK2, CxCl10, BCAT1, HID1, PRDM16, MADD, PXDN, GALE | 10 |
| Li et al. [73] | 232 | Saliva samples | BMI | - | 28,587 |
| Aslibekyan et al. [74] |
991 Replicatin: 2,377, 2,097 |
CD4+ T-cells; Replicatin in whole blood samples | BMI, WC | CPT1A, PHGDH, CD38 | 8 (BMI) and 5 (WC) |
The full name of the abbreviations can be found in the abbreviate table