Table S1. Genes contributing to the enrichment scores of GSEA for gene-sets down-regulated in adipose tissue from diabetic compared with non-diabetic co-twins.
Gene-set name Genes contributing to the enrichment score
ALDH9A1, ECHS1, HADHA, AUH, ABAT, HSD17B4, HADHB, HMGCS1, DBT, PCCB, HSA00280 Valine, leucine and isoleucine degradation HIBADH, OXCT1, ALDH7A1, MCCC2, BCKDHB, ACADM, MCCC1, MCEE, PCCA, MUT, ALDH2, ACAT1, DLD, ALDH6A1, HADH, HIBCH
ALDH9A1, ECHS1, HADHA, ABAT, SUCLG2, SUCLA2, PCCB, ALDH7A1, SUCLG1, ACACB, HSA00640 Propanoate metabolism ACADM, LDHB, MCEE, ACACA, PCCA, ACSS2, MUT, ALDH2, ACAT1, ALDH6A1, HIBCH
ACO2, IDH2, SDHA, IDH3B, PCK1, MDH1, CS, CLYBL, SDHB, ACLY, IDH1, SDHD, FH, ACO1, HSA00020 Citrate cycle SUCLG2, SUCLA2, IDH3A, DLST, SUCLG1, PC, DLD
HADHA, ELOVL6, SCD, ACOX1, HSD17B12, HSA01040 Polyunsaturated fatty acid biosynthesis FADS2, ELOVL5, FADS1, PECR, FASN
ALDH9A1, ECHS1, HADHA, L2HGDH, ABAT, PDHB, HSD17B4, ALDH5A1, HMGCS1, BDH1, HSA00650 Butanoate metabolism OXCT1, ALDH7A1, PDHA1, AACS, PRDX6, ALDH2, ACAT1, HADH
ATP5J, NDUFA1, UQCRQ, ATP12A, ATP6V1E2, NDUFA4, SDHA, NDUFB6, NDUFV3, ATP6V1G1, NDUFC1, ATP5E, COX7A2, ATP5F1, ATP6V1H, ATP6V1G3, NDUFB4, NDUFA12, COX6A1, COX6C, ATP6V1D, UQCRFS1, NDUFB8, SDHB, NDUFS3, HSA00190 Oxidative phosphorylation COX7C, ATP5H, NDUFA6, NDUFS2, ATP5L, SDHD NDUFA8, NDUFB3, ATP6V1C1, NDUFS5, NDUFA9, ATP5A1, ATP5B, COX4I2, COX10, NDUFA5, ATP6V1E1, UQCRH, NDUFV2, PPA2, NDUFA10, NDUFS1, NDUFB5, UQCRB, UQCRC2, ATP5C1, NDUFAB1
ALDH9A1, ECHS1, HADHA, ADH1B, ACSL4, HSA00071 Fatty acid metabolism ACSL3, HSD17B4, HADHB, ACOX1, ADHFE1, ACSL1, GCDH, ALDH7A1, ACADSB, ACADL, ACADM, ALDH2, ACAT1, HADH
ACYP2, PCK1, MDH1, ALDH9A1, DLAT, GLO1, HSA00620 Pyruvate metabolism PDHB, LDHD, ME1, ALDH7A1, ACACB, PDHA1, PC, LDHB, ACACA, ACSS2, ALDH2, ACAT1, DLD
TAF1, TAF13, GTF2E2, GTF2H2, TBPL1, TAF12, HSA03022 Basal transcription factors GTF2IRD1, TAF2, TAF7, GTF2A1, GTF2H1, GTF2B, TAF9B, GTF2I, GTF2A2, GTF2H3, TAF9
HSA00072 Synthesis and degradation of keton bodies HMGCS1, BDH1, OXCT1, ACAT1
ACO2, IDH2, MDH1, ACLY, IDH1, FH, ACO1, HSA00720 Reductive carboxylate cycle SUCLA2, ACSS2
SUV39H1, RDH14, ALDH9A1, ECHS1, HADHA, TMLHE, HSD17B4, NSD1, DLST, GCDH, HSA00310 Lysine degradation AASDHPPT, ALDH7A1, SHMT1, PLOD2, AASS, ALDH2, ACAT1, HADH
NARS2, DLAT, ADSSL1, ABAT, PDHB, DDO, GPT, HSA00252 Alanine and aspartate metabolism DARS, PDHA1, PC, ASPA, GPT2, DLD
HSA00061 Fatty acid biosynthesis OXSM, ACACB, ACACA, FASN
Table S2. Genes contributing to the enrichment scores of GSEA for gene- sets up-regulated in adipose tissue from diabetic compared with non-diabetic co-twins.
Gene-set name Genes contributing to the enrichment score
HSA01032 Glycan structures MAN2B2, HEXB, GBA, IDS, GLB1, NEU3, FUCA1, HEXA, degradation MAN2B1, NEU1, NAGLU, GUSB, ARSB, GALNS, FUCA2, NEU4
HSA00603 Glycosphingolipid A4GALT, HEXB, NAGA, HEXA, ST8SIA1, GBGT1, GLA biosynthesis globoseries
PLAUR, SERPINA5, F5, C2, SERPINE1, SERPING1, C1S, MASP1, HSA04610 Complement and C1QC, C1R, C3, C3AR1, C7, F10, C1QB, F13A1, C1QA, C5AR1, coagulation cascades PROS1, CFH, CFD, PLAU, F2R, BDKRB2, C4BPB, C6, BDKRB1, FGB, CFB, CR1, CD55, VWF
MAN2B2, HEXB, GLB1, NEU3, FUCA1, HEXA, MAN2B1, NEU1, HSA00511 N-glycan degradation FUCA2, NEU4
CD44, CSF1, ANPEP, CD9, CD14, CSF1R, ITGA3, CD38, IL7, IL6R, CD33, CD4, HLA-DRB4, IL11RA, ITGA5, IL4R, FCER2, HSA04640 Hematopoietic cell lineage ITGAM, TNF, HLA-DRB5, HLA-DRA, TFRC, CSF2RA, FLT3LG, CD1C, CD37, HLA-DRB3, CD5, CD3E, CD2, EPO, CD8A, CR1, CD1A, CD55, CD1B, IL1B, ITGA4, CD1E, IL3, CD19, IL1R1, CD22
CTSB, TAPBP, CD74, LGMN, IFI30, HLA-DMB, CALR, RFXANK, CD4, HLA-DRB4, HLA-DMA, CTSL1, HLA-DQA2, HLA-DPB1, HSA04612 Antigen processing and CIITA, HSPA5, HLA-DRB5, HLA-DRA, IFNA1, IFNA6, HLA-DRB3, presentation CD8A, CTSS, HLA-DQA1, HLA-DQB1, HLA-DPA1, KIR2DS5, IFNA14
HSA00604 Glycosphingolipid HEXB, GLB1, B3GALT4, HEXA, ST8SIA1 biosynthesis ganglioseries
HSA00532 Glycosaminoglycan XYLT1, UST, CHPF, B3GAT3, CHST14, CHST7, CHST13, biosynthesis B3GALT6
HSA00531 Glycosaminoglycan HEXB, IDS, GLB1, HEXA, NAGLU, GUSB, ARSB, GALNS degradation
CD276, ALCAM, ICAM1, ITGB2, CLDN11, GLG1, ITGAV, NLGN2, CLDN20, HLA-DMB, CADM3, CD99, CD28, SIGLEC1, NEGR1, CD4, HLA-DRB4, HLA-DMA, CD86, CNTNAP1, PDCD1LG2, HLA- HSA04514 Cell adhesion molecules DQA2, ITGAM, HLA-DPB1, VCAN, VCAM1, HLA-DRB5, CLDN8, ICOSLG, HLA-DRA, SDC1, CTLA4, PVRL2, MADCAM1, NRXN3, CLDN15, HLA-DRB3, SPN, CD2, ITGB7, CD8A, MPZ, HLA-DQA1, HLA-DQB1, CNTN2, SELPLG, HLA-DPA1, ITGA4, SDC3, MPZL1, SDC4, CD22, PTPRC, CD80, CLDN14, CLDN23, CLDN22, CLDN18
HS3ST2, DDOST, XYLT1, ALG12, UST, GALNT6, CHPF, MAN1B1, B4GALT2, GALNT12, B3GNT1, CHST14, GCNT1, B3GNT7, HSA01030 Glycan structures GALNT10, MAN1C1, ALG3, RPN1, CHST7, EXT2, DPAGT1, biosynthesis 1 B3GNT2, CHST13, MAN1A1, GALNTL1, FUT11, GALNT9, ALG1, MGAT4B, CHST2, RPN2, B3GALT6, CHST11, ST3GAL4, MGAT5, MGAT5B, GALNT4, HS6ST1, GALNT2, MGAT1, NDST2, HS3ST1
RPS16, RPL18, RPS5, RPL10L, RPS27, RPS2, RPL18A, RPS9, RPSA, RPL28, RPS3, RPS4Y1, RPL13A, RPL13, RPS11, RPL8, HSA03010 Ribosome RPL31, RPL19, RPS26, RPL3, RPL12, RPS10, RPS8, RPS28, RPL38, RPL39, RPS24
TNFRSF11A, TNFRSF14, CSF1, CCL22, XCR1, LTBR, PDGFRA, TNFRSF1A, PDGFRB, CXCL16, CCL13, CCL18, IL18, CSF1R, CCL26, TNFRSF10D, IL7, IL6R, PLEKHO2, CCR1, IL10RA, IL12RB2, CCL19, TNFRSF11B, CCL2, TGFB1, IL11RA, PDGFB, IL10RB, VEGFB, IL4R, TGFB2, TNF, TGFB3, CCL8, CCL3, CXCR3, TNFSF8, TNFRSF12A, IL10, EDA2R, IL17RB, CSF2RA, HSA04060 Cytokine cytokine receptor TNFSF15, XCL1, TNFRSF9, IL2RG, IL12RB1, IL21R, IFNA1, interaction FLT3LG, IFNA6, TGFBR2, IL28RA, IL26, ACVR2B, IL15RA, LEP, IL2RB, GH2, EPO, OSMR, CTF1, HGF, CCR2, IL22RA2, CRLF2, TNFRSF1B, CSF2RB, IL17RA, TNFSF9, EDA, CCR4, IL1B, CLCF1, IL3, IL1R1, CCL21, CXCR4, IL29, IFNA14, IL23A, AMH, OSM, INHBB, IL5RA, CXCL12, CXCL6, CCL7, IL28A, CXCL9, GH1, FAS, IL1A
HLA-DMB, CD28, HLA-DRB4, HLA-DMA, CD86, HLA-DQA2, TNF, PTPRN, HLA-DPB1, HLA-DRB5, HLA-DRA, HLA-DRB3, HSA04940 Type 1 diabetes mellitus PRF1, HLA-DQA1, HLA-DQB1, HLA-DPA1, IL1B, CD80, FAS, IL1A, LTA, GZMB
GBA, SMPD1, GLB1, NEU3, SGMS2, SGPP2, GLA, GALC, NEU1, HSA00600 Sphingolipid metabolism SMPD4, SGPP1, ARSD, NEU4
COL6A2, LAMB2, CD44, TNXB, COL6A1, ITGB5, THBS2, SPP1, VTN, ITGA3, COL1A2, ITGAV, FNDC4, COL6A3, THBS3, FN1, ITGA5, THBS1, HSPG2, LAMB3, FNDC1, SDC1, TNC, COL5A1, HSA04512 ECM receptor interaction SV2A, LAMA2, COL3A1, COL1A1, COL4A4, COL4A6, ITGB7, DAG1, IBSP, ITGB4, LAMC2, VWF, FNDC5, ITGA4, SDC3, RELN, SDC4 IKBKE, CD14, MAPK13, SPP1, IRAK1, IRF5, MAP3K8, MAPK3, HSA04620 Toll like receptor signaling FADD, IKBKB, PIK3R2, LY96, IRF3, MAP2K2, CD86, MYD88, pathway TLR7, PIK3CG, IKBKG, PIK3R5, TRAF3, TNF, TICAM1, CCL3, LBP, MAP2K3, FOS, IFNA1, RELA, IFNA6, TLR5
Table S3. Genes differently expressed in adipose tissue from T2D discordant twin pairs (q<0.15).
Non-T2D T2D Difference Gene Symbol Probe ID p value q value mean ± SD mean ± SD (%)
ACAT1 7943605 743.5 ± 137.3 604.7 ± 91.1 -18.7 0.0005 0.135
ACVR1C 8055992 2010.2 ± 442.2 1576.0 ± 273.4 -21.6 0.0005 0.135
ADAM20 7979927 168.3 ± 24.9 146.3 ± 15.5 -13.1 0.0005 0.135
ALCAM 8081431 201.2 ± 80.8 316.8 ± 88.5 36.5 0.00098 0.144
ALDH3B1 7941961 182.2 ± 23.6 214.0 ± 18.7 14.8 0.0005 0.135
ALDH6A1 7980098 898.8 ± 170.7 729.5 ± 117.5 -18.8 0.00098 0.144
ANAPC16 7928300 449.9 ± 31.7 402.2 ± 48.7 -10.6 0.00098 0.144
ANKRD18DP 8093272 12.0 ± 1.5 13.8 ± 2.4 13.4 0.00098 0.144
APOC1 8029536 120.0 ± 22.0 162.9 ± 28.7 26.3 0.00098 0.144
ARHGAP1 7947681 1577.3 ± 109.7 1671.6 ± 106.1 5.6 0.00098 0.144
ASB1 8049657 191.2 ± 18.2 211.6 ± 21.2 9.6 0.0005 0.135
ASF1B 8034772 51.1 ± 4.4 59.6 ± 7.8 14.2 0.0005 0.135
ATPAF1 7915870 168.8 ± 16.9 151.2 ± 15.8 -10.5 0.0005 0.135
AVPR1A 7964660 239.9 ± 33.4 214.2 ± 39.3 -10.7 0.0005 0.135
AZGP1 8141374 563.2 ± 302.7 323.5 ± 155.9 -42.6 0.00098 0.144
BAD 7949067 207.6 ± 15.7 226.6 ± 11.3 8.4 0.00098 0.144
BCCIP 7931268 180.2 ± 18.6 158.5 ± 13.8 -12.1 0.0005 0.135
BRAF 8143417 844.8 ± 75.7 779.4 ± 63.4 -7.7 0.00098 0.144
C11orf68 7949540 235.0 ± 15.6 247.5 ± 10.1 5.1 0.0005 0.135
C13orf33 7968351 772.9 ± 305.7 1007.5 ± 378.8 23.3 0.00098 0.144
C14orf39 7979483 23.6 ± 7.2 17.9 ± 5.4 -24.3 0.0005 0.135
C18orf21 8020919 184.4 ± 9.4 167.0 ± 9.0 -9.4 0.00098 0.144
C1S 7953603 1692.1 ± 277.8 2024.4 ± 287.6 16.4 0.00098 0.144 C9orf95 8161839 125.5 ± 22.6 107.0 ± 18.1 -14.8 0.0005 0.135
CAPG 8053417 190.0 ± 43.6 234.6 ± 45.9 19.0 0.00098 0.144
CCDC80 8089544 2739.3 ± 553.6 3205.1 ± 500.4 14.5 0.00098 0.144
CD14 8114612 948.3 ± 484.1 1500.7 ± 622.2 36.8 0.00098 0.144
CD276 7984743 237.4 ± 33.1 288.1 ± 37.0 17.6 0.00098 0.144
CD44 7939341 1888.7 ± 357.0 2272.0 ± 318.5 16.9 0.00098 0.144
CD68 8004510 1931.7 ± 637.0 2879.1 ± 660.8 32.9 0.00098 0.144
CDC20 7900699 89.1 ± 13.2 98.4 ± 11.6 9.4 0.0005 0.135
CHPT1 7958000 1205.7 ± 124.6 1102.7 ± 74.3 -8.5 0.00098 0.144
CLEC3B 8079305 555.9 ± 111.9 675.9 ± 112.9 17.8 0.0005 0.135
CLN3 8000543 262.1 ± 22.9 297.8 ± 26.2 12.0 0.0005 0.135
COMMD5 8153911 144.5 ± 13.5 161.1 ± 8.1 10.3 0.00098 0.144
COPS2 7988605 1343.5 ± 97.9 1182.2 ± 123.9 -12.0 0.0005 0.135
CRB1 7908508 40.9 ± 3.6 36.8 ± 2.5 -9.9 0.00098 0.144
CRBN 8085081 738.9 ± 56.7 677.9 ± 61.2 -8.3 0.00098 0.144
CRELD2 8073949 130.8 ± 9.5 144.0 ± 5.4 9.1 0.0005 0.135
CSE1L 8063283 626.8 ± 46.2 585.3 ± 33.0 -6.6 0.0005 0.135
CTBP2 7936904 182.7 ± 8.3 193.3 ± 11.0 5.5 0.0005 0.135
CTDSPL2 7983335 603.0 ± 55.9 550.3 ± 31.5 -8.7 0.00098 0.144
CTSB 8149330 2508.5 ± 557.8 3148.2 ± 544.4 20.3 0.0005 0.135
CTSD 7945666 2485.5 ± 390.8 3070.1 ± 470.5 19.0 0.00098 0.144
CTSZ 8067279 718.1 ± 129.3 849.7 ± 110.7 15.5 0.0005 0.135
CYP27A1 8048432 210.8 ± 43.1 268.5 ± 51.2 21.5 0.0005 0.135
DDB2 7939738 415.4 ± 42.4 499.5 ± 84.4 16.8 0.0005 0.135
DLD 8135464 753.0 ± 145.6 613.0 ± 92.7 -18.6 0.00098 0.144
DMRT2 8154047 103.6 ± 19.1 87.4 ± 15.2 -15.7 0.00098 0.144 DNA2 7934026 73.9 ± 15.9 62.0 ± 12.8 -16.1 0.0005 0.135
DNM1 8158183 380.7 ± 78.4 501.3 ± 116.1 24.1 0.0005 0.135
DPP6 8137485 80.8 ± 56.0 58.4 ± 10.5 -27.8 0.00098 0.144
EGR2 7933872 116.0 ± 21.1 142.2 ± 30.4 18.4 0.0005 0.135
EMP3 8030007 579.1 ± 132.9 759.0 ± 127.4 23.7 0.0005 0.135
EVC2 8099144 64.2 ± 4.4 72.0 ± 6.1 10.8 0.0005 0.135
F5 7922174 74.9 ± 41.3 91.8 ± 41.3 18.4 0.0005 0.135
FAM118A 8073752 157.2 ± 48.6 177.9 ± 63.6 11.6 0.00098 0.144
FAM174A 8107119 146.1 ± 15.4 129.8 ± 12.0 -11.1 0.00098 0.144
FAM86B1 8149389 269.6 ± 26.9 288.8 ± 28.4 6.6 0.0005 0.135
FASTK 8143863 309.9 ± 26.3 328.4 ± 28.3 5.6 0.00098 0.144
FBXO11 8052024 664.4 ± 57.8 592.6 ± 58.1 -10.8 0.0005 0.135
FBXO34 7974473 242.6 ± 16.9 226.0 ± 25.2 -6.8 0.0005 0.135
FBXO4 8105111 181.0 ± 17.5 166.9 ± 17.5 -7.8 0.0005 0.135
FCGBP 8036787 91.2 ± 23.0 146.5 ± 52.7 37.8 0.0005 0.135
FHL3 7915147 140.3 ± 15.7 158.3 ± 12.8 11.3 0.0005 0.135
FOXRED2 8075785 119.3 ± 15.4 149.3 ± 24.3 20.1 0.00098 0.144
FRYL 8100251 716.9 ± 51.7 651.6 ± 34.3 -9.1 0.00098 0.144
FRZB 8057506 143.4 ± 51.6 114.3 ± 33.6 -20.3 0.0005 0.135
FXYD5 8027778 439.7 ± 73.8 527.2 ± 96.8 16.6 0.0005 0.135
GABRB2 8115651 87.8 ± 38.9 142.0 ± 75.1 38.2 0.00098 0.144
GHDC 8015575 119.0 ± 8.8 130.0 ± 7.4 8.5 0.0005 0.135
GOLGA8IP 7981859 161.7 ± 12.4 147.0 ± 12.8 -9.1 0.0005 0.135
GOLGA8IP 7986947 163.1 ± 12.3 148.3 ± 13.6 -9.1 0.00098 0.144
GPNMB 8131844 1728.9 ± 510.0 2421.2 ± 510.0 28.6 0.00098 0.144
GPR137B 7910680 380.4 ± 102.6 505.7 ± 124.9 24.8 0.0005 0.135 GPT2 7995362 321.7 ± 74.4 255.4 ± 72.5 -20.6 0.00098 0.144
GRAMD1B 7944769 62.3 ± 8.5 72.5 ± 10.4 14.0 0.0005 0.135
GSTP1 7941936 2209.6 ± 288.1 2443.2 ± 261.4 9.6 0.00098 0.144
HADH 8096753 1355.3 ± 231.6 1120.5 ± 212.4 -17.3 0.00098 0.144
HIBCH 8057719 403.4 ± 50.3 321.4 ± 38.1 -20.3 0.0005 0.135
HIST1H2BM 8117594 108.8 ± 35.8 160.8 ± 42.7 32.3 0.0005 0.135
HIST1H3B 8124388 95.5 ± 30.0 127.4 ± 40.5 25.0 0.0005 0.135
HM13 8061542 428.9 ± 47.6 491.0 ± 50.9 12.6 0.0005 0.135
HMGA1 8180308 214.3 ± 20.5 241.9 ± 25.4 11.4 0.0005 0.135
HNRNPA3 7971920 1198.9 ± 119.9 1044.2 ± 110.3 -12.9 0.0005 0.135
HNRNPA3 8046590 915.0 ± 94.9 794.5 ± 75.4 -13.2 0.0005 0.135
HNRNPA3 8080991 1170.3 ± 132.9 1019.5 ± 100.3 -12.9 0.0005 0.135
HOMER3 8035566 239.1 ± 16.7 260.5 ± 19.4 8.2 0.00098 0.144
HPS3 8083282 573.0 ± 63.9 639.8 ± 80.3 10.4 0.00098 0.144
HS3ST2 7994052 118.3 ± 15.3 148.1 ± 26.8 20.1 0.00098 0.144
IMMP1L 7947332 79.6 ± 8.7 66.4 ± 9.6 -16.6 0.00098 0.144
ISCA1 8112331 1329.5 ± 405.7 1147.2 ± 167.8 -13.7 0.00098 0.144
ISLR 7984813 531.9 ± 97.7 701.8 ± 96.6 24.2 0.0005 0.135
ITIH5 7931977 2669.6 ± 399.0 3046.0 ± 382.1 12.4 0.0005 0.135
KCTD7 8133167 340.2 ± 31.5 359.5 ± 32.9 5.3 0.00098 0.144
KIAA0922 8097867 663.3 ± 147.9 553.1 ± 141.9 -16.6 0.0005 0.135
KIAA0930 8076690 335.2 ± 68.6 451.2 ± 70.6 25.7 0.0005 0.135
KIAA1109 8097148 909.2 ± 71.0 852.2 ± 45.9 -6.3 0.00098 0.144
KRCC1 8053648 308.3 ± 32.2 270.9 ± 27.3 -12.1 0.00098 0.144
LAMB2 8087337 942.6 ± 79.7 1040.8 ± 78.7 9.4 0.0005 0.135
LDB2 8099524 1488.7 ± 184.8 1300.3 ± 114.3 -12.7 0.0005 0.135 LGALS9C 8005458 180.6 ± 39.1 237.2 ± 49.2 23.9 0.00098 0.144
LGI2 8099685 98.0 ± 35.5 139.9 ± 38.3 42.7 0.0005 0.135
LIMK1 8133413 184.8 ± 20.0 213.1 ± 23.3 13.3 0.00098 0.144
LOC441204 8131965 253.8 ± 37.8 273.3 ± 41.9 7.1 0.0005 0.135
LOC441666 8069494 61.9 ± 7.0 51.1 ± 8.7 -17.5 0.0005 0.135
LPAR1 8163257 323.6 ± 47.2 379.0 ± 42.5 14.6 0.0005 0.135
LRRK1 7986463 217.7 ± 34.1 267.8 ± 40.2 18.7 0.0005 0.135
LSM6 8097679 306.2 ± 39.3 256.6 ± 39.4 -16.2 0.00098 0.144
LYPLAL1 7909801 183.6 ± 11.0 152.7 ± 17.3 -16.8 0.0005 0.135
LYRM5 7954460 665.1 ± 61.7 578.3 ± 41.1 -13.1 0.00098 0.144
MAN2B2 8093916 499.0 ± 71.0 574.3 ± 69.6 13.1 0.00098 0.144
MAP1B 8106098 1421.8 ± 369.6 1732.6 ± 390.4 17.9 0.0005 0.135
MICB 8118116 116.2 ± 13.0 129.3 ± 11.8 10.1 0.00098 0.144
MIR30C2 8127498 139.2 ± 18.0 111.9 ± 15.3 -19.6 0.00098 0.144
MLXIP 7959361 636.5 ± 66.3 707.1 ± 87.6 11.1 0.00098 0.144
MYL9 8062312 2068.1 ± 300.8 2301.1 ± 190.0 10.1 0.0005 0.135
MYOF 7935058 1159.5 ± 192.6 1342.1 ± 186.8 13.6 0.0005 0.135
NAGA 8076403 247.0 ± 39.3 287.6 ± 41.9 14.1 0.0005 0.135
NEMF 7978866 469.4 ± 28.5 413.7 ± 33.5 -11.9 0.00098 0.144
NFATC4 7973709 129.7 ± 6.1 139.1 ± 7.1 6.8 0.0005 0.135
NIPSNAP3B 8157027 305.5 ± 62.4 245.9 ± 46.6 -19.5 0.0005 0.135
NOX4 7950933 201.1 ± 37.8 259.8 ± 57.4 22.6 0.0005 0.135
NPC2 7980146 1734.3 ± 309.1 2125.3 ± 312.0 18.4 0.0005 0.135
NR3C1 8114814 1131.4 ± 89.7 1031.9 ± 101.8 -8.8 0.00098 0.144
NUP88 8011832 702.9 ± 70.1 641.1 ± 60.2 -8.8 0.00098 0.144
NXF5 8174105 37.9 ± 4.2 32.6 ± 3.3 -14.0 0.00098 0.144 ODZ3 8098441 495.0 ± 101.4 414.1 ± 82.5 -16.4 0.0005 0.135
OLFML2B 7921882 380.1 ± 119.6 477.1 ± 107.3 20.3 0.00098 0.144
PAIP2 8108424 1806.8 ± 154.9 1657.8 ± 95.6 -8.2 0.00098 0.144
PAIP2B 8052940 195.3 ± 33.7 166.5 ± 27.9 -14.7 0.0005 0.135
PARN 7999562 746.7 ± 41.5 708.6 ± 36.1 -5.1 0.0005 0.135
PCLO 8140620 186.8 ± 106.7 132.1 ± 97.8 -29.3 0.00098 0.144
PDS5A 8099926 951.1 ± 42.9 890.5 ± 55.1 -6.4 0.0005 0.135
PFN1P2 7904974 2780.5 ± 278.6 2973.1 ± 346.3 6.5 0.0005 0.135
PKM2 7990151 859.0 ± 121.3 1035.5 ± 149.4 17.0 0.0005 0.135
PLBD2 7958989 532.6 ± 99.4 666.7 ± 92.0 20.1 0.0005 0.135
PLCB1 8060854 449.6 ± 83.5 379.8 ± 65.0 -15.5 0.0005 0.135
PLD3 8028791 1210.8 ± 233.5 1504.9 ± 221.4 24.3 0.00098 0.144
PLXNA1 8082314 326.0 ± 33.7 365.3 ± 40.8 10.8 0.0005 0.135
PNPLA8 8142307 301.5 ± 30.3 264.9 ± 27.5 -12.1 0.00098 0.144
PPL 7999253 256.6 ± 50.8 318.0 ± 47.8 19.3 0.00098 0.144
PPT1 7915286 775.2 ± 132.4 883.6 ± 130.7 12.3 0.00098 0.144
PSAP 7934196 3180.6 ± 377.5 3475.9 ± 301.8 8.5 0.00098 0.144
PTGES 8164580 227.0 ± 29.0 281.6 ± 38.0 19.4 0.0005 0.135
PTGES3 7964250 877.8 ± 74.1 795.6 ± 85.5 -9.4 0.0005 0.135
RAB13 7920422 587.0 ± 49.0 641.7 ± 42.9 8.5 0.00098 0.144
RB1 7969017 758.0 ± 59.6 674.8 ± 31.5 -11.0 0.0005 0.135
RNF125 8020806 391.1 ± 62.2 319.9 ± 28.6 -18.2 0.0005 0.135
RPLP1 8180355 2132.9 ± 199.9 2356.3 ± 178.7 9.5 0.00098 0.144
RRAS 8038407 3140.5 ± 250.9 3383.9 ± 194.3 7.2 0.0005 0.135
RUSC1 7905999 141.7 ± 11.0 158.2 ± 12.7 10.5 0.0005 0.135
S100A11 7920128 2981.9 ± 465.2 3391.6 ± 347.5 12.1 0.0005 0.135 S100A4 7920271 493.7 ± 145.1 757.0 ± 136.5 34.8 0.0005 0.135
S100B 8071036 775.0 ± 274.1 608.3 ± 212.1 -21.5 0.00098 0.144
SAA2 7946983 1359.1 ± 1105.6 855.1 ± 667.2 -37.1 0.0005 0.135
SC5DL 7944656 799.2 ± 209.7 626.7 ± 130.0 -21.6 0.0005 0.135
SCAMP2 7990417 889.7 ± 116.8 1012.8 ± 142.3 12.2 0.00098 0.144
SCN4A 8017521 324.8 ± 51.9 273.8 ± 36.5 -15.7 0.00098 0.144
SCYL2 7957806 705.2 ± 58.8 659.1 ± 62.2 -6.5 0.0005 0.135
SDF4 7911422 369.5 ± 28.3 396.7 ± 30.5 6.9 0.00098 0.144
SELM 8075462 960.3 ± 126.1 1082.2 ± 107.7 11.3 0.0005 0.135
SEMA3G 8087907 449.3 ± 65.6 569.2 ± 63.5 21.1 0.0005 0.135
SERPINA5 7976488 74.9 ± 17.0 95.5 ± 12.2 21.6 0.00098 0.144
SERPING1 7940028 3040.5 ± 311.0 3382.5 ± 242.0 10.1 0.00098 0.144
SHOC2 7930470 1035.0 ± 57.1 957.8 ± 63.5 -7.5 0.00098 0.144
SLC10A3 8176109 241.7 ± 14.1 256.8 ± 14.0 5.9 0.00098 0.144
SLC24A6 7966600 233.7 ± 13.3 262.5 ± 22.6 11.0 0.0005 0.135
SLC36A1 8109350 228.1 ± 51.5 279.8 ± 53.7 18.5 0.00098 0.144
SLC37A2 7944931 145.9 ± 44.6 201.3 ± 48.0 27.5 0.0005 0.135
SLC7A4 8074701 143.7 ± 33.4 174.3 ± 48.3 17.5 0.0005 0.135
SMCHD1 8019885 627.5 ± 92.3 556.0 ± 39.0 -11.4 0.0005 0.135
SNHG12 7914202 271.7 ± 36.4 328.8 ± 52.1 17.4 0.0005 0.135
SNTG2 8039977 133.5 ± 15.4 113.4 ± 12.8 -15.1 0.00098 0.144
SSFA2 8046726 918.5 ± 62.2 827.2 ± 54.0 -9.9 0.0005 0.135
ST14 7945204 111.5 ± 27.1 155.4 ± 34.4 28.3 0.00098 0.144
STARD3 8006877 342.3 ± 35.5 381.2 ± 27.0 10.2 0.00098 0.144
STK32B 8093858 63.9 ± 10.9 80.2 ± 16.0 20.2 0.00098 0.144
SYPL1 8142110 986.9 ± 72.2 919.6 ± 56.0 -6.8 0.00098 0.144 TARBP2 7955829 139.0 ± 11.0 149.8 ± 11.7 7.2 0.0005 0.135
TET1 7927876 210.0 ± 24.7 177.6 ± 32.4 -15.4 0.00098 0.144
TNFRSF11A 8021528 102.5 ± 20.0 127.9 ± 20.3 19.9 0.0005 0.135
TNFRSF14 7911754 336.2 ± 37.5 385.7 ± 27.4 12.8 0.00098 0.144
TNFSF12-13 8004464 369.0 ± 23.3 397.5 ± 19.6 7.2 0.0005 0.135
TRAF7 7992529 217.0 ± 16.4 249.1 ± 15.6 12.9 0.0005 0.135
TRAPPC8 8022767 253.4 ± 18.6 229.4 ± 19.6 -9.5 0.0005 0.135
TREM2 8126279 104.0 ± 52.1 154.3 ± 43.4 32.6 0.0005 0.135
TRMT1L 7922870 385.7 ± 33.7 353.9 ± 30.1 -8.2 0.00098 0.144
TSGA10 8054166 117.2 ± 27.3 84.4 ± 20.8 -27.9 0.0005 0.135
TSPAN4 7937518 718.7 ± 61.6 795.4 ± 61.9 9.6 0.00098 0.144
TTLL7 7917199 271.0 ± 48.6 218.6 ± 30.5 -19.3 0.00098 0.144
UCHL1 8094778 738.9 ± 253.4 977.9 ± 226.9 24.4 0.0005 0.135
USP34 8052443 1002.7 ± 58.1 925.3 ± 78.7 -7.7 0.0005 0.135
VPS37C 7948504 168.5 ± 8.3 184.2 ± 11.9 8.5 0.0005 0.135
WWP2 7996976 254.4 ± 21.3 276.0 ± 23.5 7.8 0.00098 0.144
ZBTB7A 8032755 427.6 ± 16.4 457.2 ± 27.1 6.5 0.00098 0.144
ZNF501 8079229 133.3 ± 20.2 116.5 ± 13.6 -12.6 0.0005 0.135
ZNF613 8030871 136.8 ± 13.2 123.0 ± 10.6 -10.0 0.0005 0.135
ZNF655 8134631 387.3 ± 29.8 365.7 ± 28.6 -5.6 0.00098 0.144
ZNF92 8133089 146.8 ± 17.6 126.4 ± 10.8 -13.9 0.00098 0.144 T2D; type 2 diabetic Table S4. Post-hoc power calculations for genome-wide mRNA expression and DNA methylation analyses in discordant twins. The power to detect a 5% difference in mRNA expression in 12 twin pairs and 3% points difference in DNA methylation in 14 twin pairs is calculated based on the actual average effect size in our study. Also, the number of twin pairs needed to reach >80% power is presented. Power was calculated using G*Power Version 3.1.5.
Standardized effect size Power in our study (%) Twin pairs needed for 80% power (n)
mRNA expression 0.51 31 38
DNA methylation 0.52 38 36
Table S5. Differentially expressed obesity susceptibility genes in adipose tissue from discordant twins (p<0.05). If present, differences in DNA methylation (p<0.05 and β>3% points difference) are shown. The SNP ID and location related to the genes are presented (data from published GWAS at www.genome.gov/gwastudies).
GWAS data mRNA expression DNA methylation
Gene Difference Non-T2D mean Difference Symbol SNP ID SNP localization Disease/Trait T2D mean ± SD p value Probe ID T2D-non-T2D ± SD (%) (% points)
rs2820464 307 kb downstream Waist-hip ratio rs11118316 271 kb downstream Visc./subc. adipose tissue ratio LYPLAL1 rs12022722 265 kb downstream Visc./subc. adipose tissue ratio 183.6 ± 11.0 152.7 ± 17.3 -16.8 0.0005 rs4846567 365 kb downstream Waist-hip ratio rs2605100 258 kb downstream Adiposity
HMGA1 rs206936 89 kb downstream BMI 214.3 ± 20.5 241.9 ± 25.4 12.9 0.0005
cg21646032 -3.2 RARB rs1435703 Intron Obesity (extreme) 78.5 ± 21.5 68.5 ± 22.3 -12.7 0.002 cg23518541 3.9
rs607541 Intron Obesity-related traits SQRDL 333.5 ± 45.5 367.9 ± 47.8 10.3 0.003 cg01626885 -3.2 rs12594515 1.6 kb downstream Waist circumference/Weight
HMGA1 rs206936 89 kb downstream BMI 205.1 ± 20.4 229.1 ± 23.7 11.7 0.005
PCSK1 rs261967 81 kb upstream BMI 26.3 ± 2.4 28.7 ± 3.8 9.0 0.005
DNM3 rs1011731 Intron Waist-hip ratio 262.6 ± 45.5 218.5 ± 22.4 -16.8 0.007 rs13130484 447 kb upstream Obesity/BMI GNPDA2 rs348495 456 kb upstream BMI 150.3 ± 18.6 133.5 ± 19.3 -11.2 0.009 rs10938397 454 kb upstream Obesity/BMI
rs1516725 Intron Obesity/BMI ETV5 rs9816226 7.6 kb upstream Obesity/BMI 131.7 ± 32.4 163.5 ± 38.7 24.1 0.01 rs7647305 7.4 kb upstream BMI/Weight
SULT1A2 rs7359397 275 kb upstream BMI 217.5 ± 68.4 264.3 ± 78.9 21.5 0.01
STAB1 rs6784615 23 kb upstream Waist-hip ratio 448.9 ± 153.3 608.5 ± 202.9 35.5 0.02
rs7745274 Intron Waist-hip ratio RSPO3 391.8 ± 156.4 321.7 ± 129.0 -17.9 0.02 cg25671837 -3.2 rs9491696 Intron Waist-hip ratio
VEGFA rs6905288 4.6 kb downstream Waist-hip ratio 767.7 ± 192.1 672.0 ± 173.1 -12.5 0.02 cg25373579 3.5
rs7586879 Intron BMI rs10182181 8.2 kb upstream Obesity rs2033654 Intron BMI ADCY3 419.5 ± 38.6 455.9 ± 45.5 8.7 0.02 rs13407913 Intron BMI rs6545814 Intron BMI rs713586 16 kb upstream BMI
LRP1B rs2890652 71 kb upstream BMI 109.9 ± 68.2 74.6 ± 45.3 -32.1 0.03
MAF rs1424233 48 kb upstream Obesity 273.9 ± 46.7 319.5 ± 71.9 16.7 0.03
MTIF3 rs4771122 Intron BMI 385.8 ± 31.5 356.4 ± 44.4 -7.6 0.03
NUDT3 rs206936 Intron BMI 763.8 ± 42.5 793.1 ± 33.0 3.8 0.03 TMEM212 rs6794092 2.8 kb upstream BMI 30.6 ± 3.2 34.5 ± 4.1 12.8 0.03
rs887912 834 kb upstream Obesity/BMI FANCL 144.7 ± 22.4 129.4 ± 12.1 -10.6 0.03 rs6731302 365 kb upstream Obesity
rs11088859 Intron Obesity NCAM2 44.2 ± 6.1 39.6 ± 5.9 -10.4 0.03 rs3819055 1.9 Mb downstream Visc. fat
rs13078807 Intron Obesity/BMI CADM2 rs2324999 35 kb downstream Subc. adipose tissue 402.0 ± 102.5 326.1 ± 124.3 -18.9 0.04 rs13323436 Intron Visc. fat
rs2943640 502 kb downstream Visc./subc. adipose tissue ratio IRS1 337.7 ± 91.2 280.5 ± 50.8 -16.9 0.04 rs2943650 490 kb downstream Adiposity
LRRFIP1 rs11680012 missense Adiposity 137.7 ± 21.9 160.3 ± 26.3 16.4 0.04 cg04862290 4.1
rs10789336 90 kb upstream Obesity/BMI rs2568958 17 kb upstream Obesity/BMI/Weight rs7531118 89 kb upstream Obesity NEGR1 rs3101336 2.7 kb upstream Obesity/Obesity (extreme) 339.1 ± 50.7 370.7 ± 56.0 9.3 0.04 rs1993709 90 kb upstream Obesity (extreme) rs990871 75 kb upstream Subc. adipose tissue rs2815752 64 kb upstream BMI
PTER rs10508503 179 kb upstream Obesity 514.2 ± 73.2 469.2 ± 74.1 -8.8 0.04
SLC39A8 rs13107325 missense BMI 306.3 ± 63.8 339.0 ± 62.3 10.7 0.04
ZNF248 rs7474896 83 kb downstream Obesity (extreme) 131.9 ± 16.3 120.3 ± 11.7 -8.8 0.04
Table S6. Differentially expressed type 2 diabetes susceptibility genes in adipose tissue from discordant twins (p<0.05). If present, differences in DNA methylation (p<0.05 and β>3% points difference) are shown. The SNP ID and location related to the genes are presented (data from published GWAS at www.genome.gov/gwastudies).
GWAS data mRNA expression DNA methylation
Gene Difference Non-T2D mean ± Difference T2D-non- Symbol SNP ID SNP localization Disease/Trait T2D mean ± SD p value Probe ID SD (%) T2D (% points)
rs10814916 Intron T2D GLIS3 97.3 ± 12.1 107.6 ± 15.9 10.5 0.003 rs7041847 Intron T2D
PCNXL2 rs12027542 Intron T2D 167.9 ± 16.9 186.4 ± 15.5 11.0 0.009
VEGFA rs9472138 58 kb downstream T2D 767.7 ± 192.1 672.0 ± 173.1 -12.5 0.02 cg25373579 3.5
rs13081389 40 kb upstream T2D PPARG rs17036101 52 kb upstream T2D 2811.6 ± 416.2 2504.1 ± 334.0 -10.9 0.03 rs1801282 missense T2D
rs4760790 83 kb upstream T2D TSPAN8 39.9 ± 16.0 33.8 ± 11.3 -15.3 0.03 rs7961581 111 kb upstream T2D
RBMS1 rs7593730 Intron T2D 1149.4 ± 117.2 1100.5 ± 106.4 -4.3 0.03
ZFAND6 rs11634397 1.5 kb downstream T2D 641.0 ± 53.4 586.1 ± 64.9 -8.6 0.03
rs7578326 575 kb downstream T2D IRS1 337.7 ± 91.2 280.5 ± 50.8 -16.9 0.04 rs2943641 502 kb downstream T2D and other traits Table S7. JASPAR motif search results in the set of differentially expressed genes between diabetic and non-diabetic twins.
Transcription Sample Background Sample Matrix ID Z score p value Adj. p value Sample SD factor average average size
KLF4 MA0039.2 4.596 2.04e-06 0.00026 0.93 0.91 0.055 195
SP1 MA0079.2 4.409 4.93e-06 0.00064 0.94 0.92 0.049 195
PAX5 MA0014.1 3.882 4.86e-05 0.0063 0.84 0.84 0.032 195
EGR1 MA0162.1 3.757 8.23e-05 0.011 0.87 0.85 0.048 195
INSM1 MA0155.1 3.737 8.89e-05 0.012 0.87 0.86 0.039 195
Table S8. Difference in mRNA expression of six candidate genes in non-obese subjects with NGT (BMI<30 kg/m2) compared with non-obese subjects with T2D (BMI<30 kg/m2).
NGT (n=40) T2D (n=28) Gene p value Mean ± SD Mean ± SD
ELOVL6 1.0 ± 1.9 0.3 ± 0.5 0.001
GYS2 1.0 ± 1.3 0.3 ± 0.2 0.0001
FADS1 1.0 ± 0.6 0.6 ± 2.1 0.02
SPP1 1.0 ± 1.9 1.7 ± 2.1 0.01
CCL18 1.0 ± 1.3 2.3 ± 4.2 0.02
IL1RN 1.0 ± 1.9 1.4 ± 1.6 0.006
Supplementary table 9. Clinical characteristics of subjects with NGT divided in two groups based on BMI (non-obese = BMI<30 kg/m2 and obese = BMI>30 kg/m2).
Unrelated subjects for validation of differentially expressed genes
Non-obese NGT Obese NGT
N (male/female) 40 (15/25) 30 (17/13)
Age (years) 55 ± 6 52 ± 8
BMI (kg/m2) 25.0 ± 2.7 35.3 ± 3.1*
Fasting plasma glucose (mmol/l) 5.5 ± 0.5 5.7 ± 0.5*
2-hour glucose (mmol/l) 5.8 ± 1.3 6.3 ± 1.2
HbA1c (%) 5.5 ± 0.3 5.5 ± 0.4
HbA1c (mmol/mol) 37 ± 3.3 37 ± 4.4 Data are shown as mean ± SD. * p<0.05 compared with non-obese. Supplementary table 10. Spearman correlations between expression of candidate genes and BMI, fasting glucose levels and 2-hour glucose in subjects with NGT (n=70).
Gene BMI (kg/m2) Fasting plasma glucose (mmol/l) 2-hour glucose (mmol/l)
ELOVL6 rho=-0.23, p=0.055 rho=-0.25, p=0.042 rho=-0.16, p=0.190
GYS2 rho=-0.29, p=0.016 rho=-0.21, p=0.09 rho=-0.14, p=0.246
FADS1 rho=-0.29, p=0.016 rho=0.005, p=0.964 rho=-0.38, p=0.001
SPP1 (OPN) rho=0.41, p=0.001 rho=0.31, p=0.009 rho=-0.14, p=0.246
CCL18 rho=0.25, p=0.035 rho=0.23, p=0.061 rho=0.19, p=0.113
IL1RN rho=0.46, p<0.001 rho=0.31, p=0.01 rho=0.23, p=0.055 Bold numbers point to results with p<0.05. Table S11. CpG-sites with differential DNA methylation (p<0.05) in adipose tissue from 14 MZ twin pairs discordant for type 2 diabetes. SNP probes; CpG-sites directly affected by a SNP with MAF >5% in Europeans (based on the lists generated by Chen et al, Epigenetics 2013). Cross- reactive probes; maximum number of bases (≥47) matched to cross-reactive targets as reported by Chen et al (Epigenetics 2013). Excel-file
Table S12. CpG-sites with differential DNA methylation (q<0.15) in adipose tissue from 28 diabetic versus 28 non-diabetic subjects (case- control cohort 2). P<0.05 in discordant twins; sites having a difference in the same direction for diabetics versus non-diabetics in discordant twins and case-control cohort 2. SNP probes; CpG-sites directly affected by a SNP with MAF >5% in Europeans (based on the lists generated by Chen et al, Epigenetics 2013). Cross-reactive probes; maximum number of bases (≥47) matched to cross-reactive targets as reported by Chen et al (Epigenetics 2013). Excel-file
Table S13. KEGG pathways with enrichment of genes that exhibit differential DNA methylation in adipose tissue from 28 diabetic compared with 28 non-diabetic subjects (case-control cohort 2).
Observed Expected Ratio Pathway Raw Adjusted Pathway class number of number of observed/ (total number of genes in pathway) p value p value genes genes expected
Pathways in cancer (325) Cancers 160 109.14 1.47 3.18x109 7.00x107
7 5 Regulation of actin cytoskeleton (211) Cell motility 106 70.85 1.50 3.91x10 3.10x10
7 5 Axon guidance (129) Development 71 43.32 1.64 4.23x10 3.10x10
6 5 Focal adhesion (200) Cell communication 100 67.16 1.49 1.09x10 6.00x10
6 Cell adhesion molecules (130) Signaling molecules and interaction 68 43.65 1.56 7.96x10 0.0003
5 Bacterial invasion of epithelial cells (70) Infectious diseases 41 23.51 1.74 1.55x10 0.0005
5 Fc gamma R-mediated phagocytosis (93) Immune system 51 31.23 1.63 1.96x10 0.0005
5 Calcium signaling pathway (176) Signal transduction 86 59.10 1.46 1.85x10 0.0005
5 Endocytosis (200) Transport and catabolism 95 67.16 1.41 2.94x10 0.0006
Phosphatidylinositol signaling system (78) Signal transduction 41 26.19 1.57 0.0004 0.0059
Chemokine signaling pathway (189) Immune system 86 63.47 1.36 0.0004 0.0059
ECM-receptor interaction (85) Signaling molecules and interaction 44 28.54 1.54 0.0004 0.0059
T cell receptor signaling pathway (108) Immune system 53 36.27 1.46 0.0006 0.0083
Wnt signaling pathway (149) Signal transduction 69 50.03 1.38 0.0008 0.0098 Glycosaminoglycan biosynthesis - chondroitin Glycan biosynthesis and 15 7.39 2.03 0.0010 0.0116 sulfate (22) metabolism
Leukocyte transendothelial migration (115) Immune system 54 38.62 1.40 0.0020 0.0163
MAPK signaling pathway (267) Signal transduction 112 89.66 1.25 0.0025 0.0196
Natural killer cell mediated cytotoxicity (122) Immune system 56 40.97 1.37 0.0031 0.0235
VEGF signaling pathway (75) Signal transduction 37 25.19 1.47 0.0034 0.0249
GnRH signaling pathway (100) Endocrine system 46 33.58 1.37 0.0065 0.0415
Fc epsilon RI signaling pathway (78) Immune system 37 26.19 1.41 0.0076 0.0464 P-values have been adjusted for multiple testing using Benjamini-Hochberg. Only relevant enriched pathways have been included in the table.
Table S14. Differentially methylated T2D susceptibility genes in case-control cohort 2.
DNA methylation Gene T2D mean ± Difference Symbol Probe ID Location NGT mean ± SD p value q value SD (% points)
ACHE cg04380800 Body 79.3 ± 3.8 82.4 ± 4.4 3.1 0.003 0.13
cg10447977 Body 24.3 ± 5.3 28.5 ± 6.2 4.2 0.002 0.12 ADAMTS9 cg25121125 TSS1500 9.0 ± 1.1 8.2 ± 1.4 -0.8 0.005 0.15
cg15464481 Body 60.0 ± 4.0 62.9 ± 3.6 3.0 0.002 0.12 ADCY5 cg25976932 Body 59.6 ± 3.5 62.3 ± 4.9 2.7 0.003 0.13
cg08786207 Body 6.3 ± 1.0 5.7 ± 1.4 -0.6 0.002 0.12
ANK1 cg21289397 3'UTR 18.3 ± 2.4 16.6 ± 3.1 -1.7 0.002 0.12
cg00176210 Body 44.5 ± 3.2 42.0 ± 4.1 -2.4 0.003 0.13
cg25466805 TSS1500 26.0 ± 2.2 23.4 ± 4.0 -2.7 0.0009 0.10
ARAP1 cg21931656 5'UTR 18.3 ± 2.4 16.3 ± 3.0 -1.9 0.003 0.13
cg00350448 Body;TSS1500 18.2 ± 1.9 17.1 ± 2.1 -1.0 0.003 0.13
cg21697198 Body 11.7 ± 1.6 10.6 ± 1.7 -1.0 0.003 0.13 BARX2 cg07355688 Body 31.6 ± 4.5 28.2 ± 4.7 -3.4 0.003 0.13 cg17753356 Body 27.2 ± 3.4 24.8 ± 4.5 -2.4 0.002 0.12
BCL11A cg16951074 Body 69.8 ± 5.4 65.3 ± 7.5 -4.5 0.003 0.13
cg23556108 Body 50.9 ± 5.7 56.2 ± 8.1 5.3 0.004 0.14
C2CD4A cg01383890 TSS200 20.3 ± 3.5 17.9 ± 3.7 -2.5 0.004 0.14
cg10426464 TSS200 6.5 ± 1.3 5.7 ± 1.3 -0.8 0.004 0.14 C2CD4B cg24181605 TSS1500 62.2 ± 3.8 65.2 ± 5.2 3.0 0.004 0.14
cg03119748 Body 54.0 ± 6.8 58.7 ± 5.9 4.8 0.0006 0.10 CAMK1D cg12273284 Body 55.2 ± 6.1 50.0 ± 7.5 -5.2 0.003 0.13
CCNE2 cg18511285 TSS1500 7.9 ± 0.9 7.2 ± 1.0 -0.7 0.004 0.14
CDC123 cg13430851 TSS1500 13.0 ± 2.1 14.8 ± 2.8 1.8 0.002 0.11
cg13405222 Body 65.7 ± 4.2 69.5 ± 4.6 3.8 0.0002 0.08 CDKAL1 cg27224478 Body 66.3 ± 4.6 70.0 ± 4.8 3.7 0.004 0.14
cg05887079 Body 39.8 ± 5.0 43.8 ± 6.4 4.0 0.002 0.12
cg09282336 Body 65.8 ± 6.0 69.8 ± 5.4 3.9 0.002 0.12
CMIP cg02597246 Body 53.8 ± 2.9 56.6 ± 4.6 2.8 0.002 0.12
cg03378645 Body 28.8 ± 2.1 31.1 ± 3.6 2.2 0.003 0.13
cg01425762 Body 59.8 ± 6.7 53.7 ± 8.6 -6.1 0.003 0.13 cg18090970 Body 84.3 ± 3.4 86.9 ± 3.3 2.6 0.002 0.12
GALNTL4 cg23678274 Body 45.1 ± 4.5 49.1 ± 6.0 4.1 0.002 0.12
cg25238480 Body 58.7 ± 5.5 63.1 ± 6.0 4.4 0.002 0.12
GLIS3 cg14641122 Body 30.4 ± 6.0 33.8 ± 6.4 3.4 0.002 0.12
HHEX cg24787755 Body 32.5 ± 3.7 29.2 ± 4.3 -3.3 0.0007 0.10
HMG20A cg25652751 5'UTR 27.8 ± 6.7 33.7 ± 9.2 5.9 0.004 0.14
cg02802391 3'UTR 38.2 ± 3.7 34.7 ± 5.5 -3.5 0.0001 0.08 HMGA2 cg05481991 TSS1500 2.9 ± 0.7 3.5 ± 0.7 0.6 0.003 0.13
HNF4A cg08314996 TSS1500 79.4 ± 2.8 77.4 ± 3.4 -2.0 0.003 0.13
cg18234011 TSS1500 5.6 ± 1.0 4.9 ± 0.9 -0.7 0.0005 0.09
IGF2BP2 cg23956648 Body 72.0 ± 3.9 69.2 ± 5.6 -2.8 0.002 0.12
cg06150454 Body 55.1 ± 3.5 52.0 ± 5.2 -3.1 0.003 0.13
cg17848496 1stExon 70.8 ± 5.4 76.6 ± 4.7 5.8 0.0001 0.08
cg00727310 1stExon 59.8 ± 6.2 65.9 ± 5.4 6.1 0.0001 0.08
IRS1 cg14283647 1stExon 67.5 ± 5.5 71.9 ± 5.0 4.5 0.0006 0.10
cg21511036 TSS200 9.6 ± 1.7 8.4 ± 1.5 -1.2 0.001 0.11
cg04129548 1stExon 66.2 ± 6.2 71.8 ± 5.2 5.6 0.001 0.11 cg00912573 1stExon 68.4 ± 5.2 73.4 ± 4.4 5.0 0.002 0.12
cg06337342 Body 65.8 ± 3.3 68.6 ± 4.1 2.8 0.0005 0.09
cg04493169 Body 39.4 ± 5.2 45.6 ± 8.1 6.2 0.002 0.12 JAZF1 cg14491535 Body 59.1 ± 4.7 54.3 ± 7.8 -4.8 0.003 0.13
cg23620719 1stExon;5'UTR 2.8 ± 0.6 2.4 ± 0.5 -0.4 0.004 0.14
KCNK16 cg02611419 3'UTR 44.3 ± 4.3 41.5 ± 5.1 -2.8 0.004 0.14
cg04894537 Body 37.0 ± 3.0 34.2 ± 4.8 -2.9 0.0002 0.08
cg19030519 Body 33.8 ± 3.9 37.7 ± 5.6 3.9 0.0003 0.09
cg05623526 Body 34.4 ± 4.0 30.6 ± 4.0 -3.8 0.0004 0.09
cg08895013 Body 38.4 ± 3.3 35.5 ± 4.5 -3.0 0.0005 0.09
cg07123182 Body 69.1 ± 3.3 72.5 ± 4.4 3.4 0.0006 0.10
KCNQ1 cg19852660 Body 18.8 ± 3.9 23.0 ± 6.0 4.2 0.001 0.11
cg19923326 Body 30.7 ± 3.5 33.8 ± 5.2 3.1 0.001 0.11
cg06294475 Body 67.6 ± 4.2 63.5 ± 6.8 -4.1 0.001 0.11
cg07979757 Body 41.1 ± 3.8 44.1 ± 4.7 3.0 0.001 0.11
cg26896748 Body 76.2 ± 6.1 80.6 ± 6.6 4.4 0.002 0.12
cg03512098 Body 52.3 ± 5.4 55.9 ± 7.0 3.6 0.002 0.12 cg15686157 Body 75.9 ± 2.6 77.9 ± 3.4 2.0 0.002 0.12
cg16419342 Body 69.2 ± 3.8 71.7 ± 3.3 2.5 0.003 0.13
cg20124933 Body 95.9 ± 1.2 96.6 ± 0.9 0.8 0.003 0.13
cg26671281 Body 52.1 ± 3.7 55.3 ± 4.2 3.1 0.003 0.13
cg19779211 TSS1500 16.7 ± 2.2 15.5 ± 2.1 -1.2 0.003 0.13
cg17333973 Body 15.0 ± 2.0 16.8 ± 2.8 1.8 0.003 0.13
cg09509144 Body 69.5 ± 4.3 72.6 ± 4.5 3.2 0.004 0.14
cg16556677 Body 51.1 ± 3.6 54.0 ± 4.9 2.9 0.004 0.14
cg02097203 Body 21.8 ± 4.2 18.6 ± 4.7 -3.1 0.004 0.14
cg14637411 Body 33.0 ± 3.4 35.6 ± 5.2 2.6 0.004 0.14
cg27119222 Body 53.9 ± 3.6 50.9 ± 5.0 -3.0 0.004 0.14
KIF11 cg25494789 Body 4.0 ± 0.9 3.4 ± 0.9 -0.6 0.005 0.15
LAMA1 cg14950072 TSS1500 14.5 ± 1.7 13.1 ± 2.2 -1.4 0.004 0.14
cg21326139 Body 54.5 ± 3.9 50.4 ± 5.7 -4.0 0.0005 0.09
cg21167046 Body 37.3 ± 2.4 34.8 ± 4.5 -2.5 0.001 0.11 MAEA cg23447233 Body 62.9 ± 6.5 57.8 ± 8.0 -5.1 0.002 0.12
cg06696815 Body 19.0 ± 3.2 17.4 ± 3.4 -1.7 0.003 0.13 cg01418351 Body 74.9 ± 3.3 72.0 ± 4.8 -3.0 0.003 0.13
cg01931028 Body 73.0 ± 5.0 76.2 ± 4.1 3.2 0.003 0.13
MARCH1 cg15498306 Body;1stExon 28.4 ± 3.7 25.6 ± 5.8 -2.8 0.003 0.13
cg07568313 Body 50.4 ± 5.1 55.1 ± 6.5 4.6 0.0001 0.08 NOTCH2 cg26196087 Body 79.4 ± 2.8 76.1 ± 5.3 -3.2 0.003 0.13
cg15083233 Body 29.0 ± 4.1 25.9 ± 4.9 -3.1 0.0009 0.10 PALM2 cg13526642 Body 25.6 ± 5.6 30.1 ± 7.5 4.5 0.005 0.15
PCNXL2 cg17894435 Body 71.7 ± 4.6 66.9 ± 5.2 -4.8 0.0002 0.08
PEPD cg25698525 1stExon;5'UTR 10.7 ± 1.3 9.7 ± 1.4 -1.0 0.004 0.14
cg16827534 5'UTR 37.2 ± 7.0 44.0 ± 9.6 6.8 0.001 0.11
PPARG cg18063278 TSS1500 29.8 ± 6.7 35.1 ± 7.5 5.3 0.003 0.13
cg25929976 TSS1500 33.0 ± 3.8 36.5 ± 5.4 3.5 0.004 0.14
R3HDML cg01255591 5'UTR;1stExon 64.1 ± 3.2 66.2 ± 3.8 2.1 0.001 0.11
cg05263743 Body 9.9 ± 1.1 8.9 ± 1.2 -1.0 0.0006 0.10
cg02772995 Body 19.6 ± 7.6 25.0 ± 10.0 5.4 0.003 0.13 RBMS1 cg18852574 Body 44.0 ± 6.2 49.7 ± 8.2 5.7 0.003 0.13
cg19506623 Body 31.7 ± 7.1 39.4 ± 11.1 7.7 0.003 0.13 RND3 cg26467069 TSS200 4.3 ± 0.8 5.1 ± 1.2 0.8 0.001 0.11
cg20059151 5'UTR;Body 33.3 ± 2.8 30.7 ± 3.8 -2.6 0.001 0.11 SLC44A3 cg11582189 Body 56.9 ± 3.1 59.8 ± 4.7 2.9 0.003 0.13
ST6GAL1 cg17448192 5'UTR 77.9 ± 3.6 73.9 ± 7.5 -4.0 0.005 0.15
cg07357827 Body 13.7 ± 3.1 17.3 ± 5.7 3.6 0.002 0.12 SYN2 cg14994183 Body 42.3 ± 4.8 39.1 ± 4.9 -3.2 0.005 0.15
cg01312265 Body 19.8 ± 5.4 23.5 ± 5.7 3.7 0.002 0.12 TCERG1L cg17004653 Body 36.8 ± 4.8 34.4 ± 5.9 -2.4 0.002 0.12
cg24788483 Body 76.1 ± 3.0 72.8 ± 4.6 -3.3 0.0001 0.08
cg03683087 Body 49.7 ± 6.5 44.8 ± 7.8 -4.9 0.002 0.12 TCF7L2 cg03339956 Body 35.2 ± 2.8 38.3 ± 4.9 3.1 0.003 0.13
cg05923857 Body 75.6 ± 3.5 73.1 ± 4.0 -2.5 0.004 0.14
THADA cg01649611 Body 38.2 ± 4.4 33.8 ± 6.1 -4.3 0.0008 0.10
cg08755736 5'UTR 70.2 ± 4.6 74.0 ± 4.7 3.7 0.002 0.12 TP53INP1 cg05266843 TSS200 8.5 ± 1.2 7.6 ± 1.4 -0.9 0.003 0.13
cg00539360 TSS1500 34.2 ± 4.9 38.1 ± 7.0 3.9 0.003 0.13 VEGFA cg18022921 TSS1500 28.9 ± 3.7 32.4 ± 6.1 3.4 0.003 0.13 WFS1 cg00433050 Body 88.3 ± 1.2 87.1 ± 1.9 -1.2 0.002 0.12
VPS26A cg01125076 5'UTR;1stExon 2.5 ± 0.5 3.0 ± 0.6 0.5 0.001 0.11
cg07493562 Body 58.4 ± 4.3 53.4 ± 5.9 -5.0 1.0E-05 0.08
WWOX cg01630032 Body 79.8 ± 5.6 72.0 ± 12.2 -7.8 0.0001 0.08
cg08122051 Body 42.6 ± 5.2 48.4 ± 7.6 5.8 0.002 0.12
cg00257775 Body 79.0 ± 6.5 73.6 ± 8.4 -5.3 0.001 0.11 ZFAND3 cg03003722 Body 43.9 ± 2.8 40.9 ± 5.1 -3.0 0.002 0.12
ZFAND6 cg18866183 5'UTR 85.5 ± 1.8 83.9 ± 2.9 -1.6 0.005 0.15
Table S15. Differentially methylated obesity susceptibility genes in case-control cohort 2.
DNA methylation Gene NGT mean ± Difference (% Symbol Probe ID Location T2D mean ± SD p value q value SD points)
ADAMTS9 cg10447977 Body 24.3 ± 5.3 28.5 ± 6.2 4.2 0.002 0.12
cg25121125 TSS1500 9.0 ± 1.1 8.2 ± 1.4 -0.8 0.005 0.147
ADCY3 cg21151432 TSS200 15.8 ± 3.2 13.3 ± 3.4 -2.5 0.0001 0.08
cg27107076 Body 29.9 ± 5.4 34.7 ± 4.9 4.8 0.0001 0.08
cg17644208 TSS1500 14.0 ± 1.9 12.9 ± 2.4 -1.1 0.001 0.10
ADCY9 cg10487659 Body 51.5 ± 4.8 55.2 ± 6.0 3.7 0.0002 0.09
cg04169369 Body 78.1 ± 3.2 80.3 ± 2.9 2.2 0.001 0.11
AIF1 cg14694191 TSS1500 51.0 ± 3.7 47.4 ± 5.7 -3.6 0.003 0.13
ANKS1B cg25188975 Body 56.7 ± 4.7 60.3 ± 5.0 3.6 0.001 0.10
cg14124788 TSS1500 9.5 ± 1.6 8.4 ± 1.4 -1.1 0.004 0.14
APOB48R cg03300649 TSS1500 69.2 ± 2.6 66.0 ± 4.4 -3.2 0.001 0.10
cg02042997 TSS200 42.2 ± 5.5 37.9 ± 6.4 -4.3 0.001 0.11
cg07337290 TSS1500 34.4 ± 4.3 30.8 ± 5.4 -3.6 0.003 0.13
cg16332159 TSS200 42.0 ± 3.3 39.2 ± 5.1 -2.8 0.004 0.14
CADM2 cg21518974 Body 80.8 ± 2.7 78.7 ± 3.0 -2.1 0.002 0.12 CDKAL1 cg13405222 Body 65.7 ± 4.2 69.5 ± 4.6 3.8 0.0002 0.08
cg27224478 Body 66.3 ± 4.6 70.0 ± 4.8 3.7 0.004 0.14
CHST8 cg15510895 5'UTR 40.7 ± 4.5 44.0 ± 6.0 3.3 0.001 0.10
CPEB4 cg07233933 Body 74.3 ± 4.5 70.4 ± 6.6 -3.9 0.001 0.10
cg04467226 TSS200 7.3 ± 0.9 6.7 ± 1.1 -0.6 0.004 0.14
DGKG cg10498502 Body 35.0 ± 2.7 32.9 ± 3.6 -2.1 0.002 0.12
cg15709989 Body 11.5 ± 4.3 14.5 ± 5.6 3.0 0.004 0.14
DNM3 cg04986015 TSS200 10.5 ± 1.2 9.2 ± 1.6 -1.3 0.0001 0.08
cg16515523 Body 4.8 ± 1.1 4.2 ± 0.8 -0.6 0.0002 0.08
cg17178220 Body 24.7 ± 6.3 30.2 ± 8.4 5.5 0.0003 0.09
cg16696002 Body 73.6 ± 4.8 69.6 ± 7.1 -4.0 0.001 0.10
ETV5 cg01270378 TSS200 5.4 ± 0.8 4.8 ± 0.9 -0.6 0.001 0.11
cg08875605 Body 59.4 ± 4.5 62.9 ± 5.8 3.5 0.002 0.12
FAT1 cg16251130 Body 65.0 ± 4.9 70.0 ± 4.4 5.0 0.00004 0.08
FBN2 cg20708842 TSS1500 22.7 ± 3.5 20.5 ± 3.8 -2.2 0.003 0.13
GALNT10 cg16319535 Body 63.8 ± 5.1 66.8 ± 5.6 3.0 0.003 0.13
GIPR cg18642271 Body 22.5 ± 2.6 20.1 ± 3.3 -2.4 0.0002 0.08
cg17351154 Body 17.9 ± 1.8 16.2 ± 2.3 -1.7 0.0003 0.09
cg19822309 Body 51.3 ± 3.8 48.0 ± 4.6 -3.3 0.001 0.10 cg16082401 Body 27.3 ± 3.0 24.6 ± 3.5 -2.7 0.001 0.10
cg18735402 Body 33.9 ± 3.7 30.9 ± 3.7 -3.0 0.003 0.13
GTF3A cg18971721 TSS200 7.0 ± 1.6 6.1 ± 1.2 -0.9 0.004 0.14
cg02654940 5'UTR;TSS200 75.8 ± 3.7 71.6 ± 6.7 -4.2 0.002 0.11
HMGA1 cg08335767 5'UTR;TSS200 43.6 ± 4.0 40.9 ± 5.4 -2.7 0.002 0.12
cg10167849 5'UTR;TSS1500 49.6 ± 5.1 46.2 ± 6.7 -3.4 0.004 0.14
cg15680902 TSS1500 11.3 ± 2.1 10.0 ± 1.9 -1.3 0.002 0.11 IL1RAP cg17184516 5'UTR 5.8 ± 0.8 5.2 ± 0.8 -0.6 0.002 0.12
INHBB cg07197823 TSS1500 4.2 ± 0.8 5.0 ± 1.9 0.8 0.003 0.13
cg17848496 1stExon 70.8 ± 5.4 76.6 ± 4.7 5.8 0.00006 0.08
cg00727310 1stExon 59.8 ± 6.2 65.9 ± 5.4 6.1 0.0001 0.08
cg14283647 1stExon 67.5 ± 5.5 71.9 ± 5.0 4.4 0.001 0.10 IRS1 cg21511036 TSS200 9.6 ± 1.7 8.4 ± 1.5 -1.2 0.001 0.11
cg04129548 1stExon 66.2 ± 6.2 71.8 ± 5.2 5.6 0.001 0.11
cg00912573 1stExon 68.4 ± 5.2 73.4 ± 4.4 5.0 0.002 0.12
cg27279652 TSS1500 8.9 ± 1.1 7.8 ± 1.4 -1.1 0.0003 0.09 ITPR2 cg13203394 Body 58.1 ± 4.7 55.1 ± 5.3 -3.0 0.001 0.11
ITPR3 cg20706766 TSS200 25.6 ± 11.5 36.0 ± 7.6 10.4 0.0002 0.08
KCNE4 cg24742614 Body 39.0 ± 3.4 42.2 ± 5.2 3.2 0.001 0.10 cg02831419 TSS1500 51.8 ± 4.7 54.7 ± 4.9 2.9 0.003 0.13
KCNMA1 cg00083188 Body 73.4 ± 5.9 66.2 ± 8.9 -7.2 0.0003 0.09
cg00404436 Body 80.8 ± 4.3 83.4 ± 4.8 2.6 0.003 0.13
cg06045319 Body 24.7 ± 3.2 27.8 ± 3.3 3.1 0.004 0.14
cg15754112 Body 38.1 ± 4.1 41.3 ± 6.1 3.2 0.004 0.14
KCTD15 cg04566826 5'UTR 28.0 ± 5.0 33.4 ± 7.7 5.4 0.0003 0.09
KREMEN1 cg02288859 Body 43.5 ± 3.5 40.6 ± 4.3 -2.9 0.001 0.10
cg26967305 3'UTR 39.7 ± 4.6 36.5 ± 6.0 -3.2 0.004 0.14
LAMA2 cg23621912 Body 41.8 ± 4.6 46.5 ± 5.8 4.7 0.003 0.13
LOC404266 cg20184247 Body;TSS1500 47.7 ± 3.6 51.3 ± 5.6 3.6 0.004 0.14
LRP1B cg15664504 Body 31.4 ± 4.7 35.0 ± 4.5 3.6 0.003 0.13
LRRFIP1 cg23393593 Body 67.1 ± 4.6 71.2 ± 4.6 4.1 0.001 0.10
cg08887327 Body 32.5 ± 3.1 30.3 ± 3.8 -2.2 0.002 0.11
cg04723343 Body 44.7 ± 4.8 48.9 ± 6.0 4.2 0.002 0.12
LY86 cg02908748 Body 80.3 ± 2.0 77.9 ± 3.5 -2.4 0.0005 0.09
cg10171489 Body 87.1 ± 2.3 85.3 ± 2.8 -1.8 0.001 0.10
cg23213758 Body 82.7 ± 3.1 80.8 ± 3.5 -1.9 0.003 0.13
MAF cg06327596 5'UTR;1stExon 5.7 ± 1.0 4.9 ± 1.0 -0.8 0.001 0.10
MFAP3 cg00244006 5'UTR;Body 5.3 ± 0.9 4.5 ± 1.0 -0.8 0.0005 0.09 MGAT1 cg01149192 5'UTR;TSS200 59.8 ± 3.8 54.6 ± 7.1 -5.2 0.0001 0.08
cg20399011 TSS1500;5'UTR 66.9 ± 5.7 61.1 ± 8.8 -5.8 0.002 0.12
cg11850468 TSS1500;5'UTR 64.6 ± 5.1 58.9 ± 9.0 -5.7 0.003 0.13
MSRA cg20679581 Body 76.1 ± 3.8 79.0 ± 2.9 2.9 0.001 0.10
cg26966828 Body 53.0 ± 7.0 47.3 ± 8.4 -5.7 0.001 0.11
cg11548083 Body 63.5 ± 3.8 60.4 ± 5.7 -3.1 0.005 0.147
NCR3 cg23484380 TSS200 49.9 ± 4.5 46.1 ± 6.0 -3.8 0.003 0.13
cg08610982 TSS200 40.6 ± 4.1 37.1 ± 5.6 -3.5 0.004 0.14
NEGR1 cg01275687 TSS1500 7.9 ± 0.8 7.4 ± 1.2 -0.5 0.003 0.13
NFE2L3 cg16882373 TSS1500 70.2 ± 4.4 65.9 ± 6.4 -4.3 0.001 0.10
cg12510708 Body 37.3 ± 3.9 34.6 ± 4.8 -2.7 0.002 0.11
cg14644871 Body 16.7 ± 1.9 15.7 ± 1.9 -1.0 0.003 0.13
NISCH cg16850945 TSS1500 53.8 ± 5.1 56.7 ± 4.7 2.9 0.003 0.13
cg08485937 TSS1500 63.9 ± 4.6 66.5 ± 4.9 2.6 0.004 0.14
NRXN3 cg16765928 Body 84.3 ± 1.7 81.6 ± 7.2 -2.7 0.0004 0.09
NUDT3 cg19494811 Body 32.5 ± 7.1 38.5 ± 10.6 6.0 0.003 0.13
PAX6 cg21764190 5'UTR 3.1 ± 0.9 3.8 ± 0.8 0.7 0.001 0.11
cg11482099 TSS1500;5'UTR 9.1 ± 1.7 7.8 ± 1.2 -1.3 0.002 0.12
cg26315277 TSS200 13.3 ± 1.6 12.0 ± 1.6 -1.3 0.003 0.13 PPM1H cg15398255 Body 79.9 ± 2.8 82.3 ± 2.9 2.4 0.0002 0.09
PPM1H cg10524576 Body 59.3 ± 4.4 55.1 ± 7.3 -4.2 0.001 0.11
PRKD1 cg07133994 Body 87.2 ± 2.8 84.3 ± 3.8 -2.9 0.00002 0.08
cg16592301 Body 85.1 ± 2.7 82.7 ± 2.8 -2.4 0.002 0.12
PTER cg27339437 TSS200 6.1 ± 1.5 5.0 ± 1.4 -1.1 0.001 0.10
RARB cg21646032 Body 72.4 ± 4.5 67.6 ± 5.6 -4.8 0.0001 0.08
cg06720425 TSS200 8.2 ± 1.1 7.5 ± 1.1 -0.7 0.004 0.14
RASAL2 cg22109530 Body;TSS200 18.5 ± 3.7 22.5 ± 5.8 4.0 0.0003 0.09
RGS6 cg21899942 Body 55.2 ± 4.7 48.7 ± 7.3 -6.5 0.00002 0.08
cg18515872 Body 47.7 ± 5.2 41.2 ± 7.0 -6.5 0.0001 0.08
ROPN1L cg11080651 Body 65.8 ± 6.0 60.1 ± 7.9 -5.7 0.001 0.11
cg00626518 TSS1500 1.4 ± 0.4 1.7 ± 0.4 0.3 0.001 0.11
cg12410225 Body 28.3 ± 2.9 25.9 ± 4.5 -2.4 0.005 0.147
RPL27A cg21975390 TSS1500 56.4 ± 3.7 53.4 ± 5.4 -3.0 0.001 0.11
cg16518015 TSS200 6.0 ± 1.4 5.0 ± 1.0 -1.0 0.003 0.13
RSPO3 cg01694400 Body 26.7 ± 6.3 32.1 ± 8.2 5.4 0.001 0.11
RTN4 cg23240589 Body 65.2 ± 3.3 67.9 ± 4.3 2.7 0.005 0.147
SEPT9 cg12098949 5'UTR;Body 36.8 ± 3.7 40.4 ± 5.1 3.6 0.001 0.10
cg05104283 Body;5'UTR 78.1 ± 4.8 81.5 ± 5.1 3.4 0.001 0.10 cg20955894 Body;5'UTR 6.9 ± 1.1 6.2 ± 1.0 -0.7 0.002 0.11
cg05184938 5'UTR;Body 7.4 ± 1.0 6.5 ± 1.2 -0.9 0.002 0.12
SLC39A8 cg21200841 TSS1500 7.9 ± 1.3 7.0 ± 1.2 -0.9 0.0005 0.09
SQRDL cg01626885 5'UTR 42.0 ± 2.8 39.0 ± 3.7 -3.0 0.001 0.10
cg09593286 TSS1500 10.1 ± 1.4 9.1 ± 1.6 -1.0 0.005 0.147
STAB1 cg01966117 TSS1500 47.4 ± 4.2 50.3 ± 3.7 2.9 0.004 0.14
SULT1A2 cg12743398 TSS1500 71.3 ± 3.2 67.5 ± 5.7 -3.8 0.001 0.10
TNNI3K cg18854765 Body 66.9 ± 5.6 62.5 ± 6.2 -4.4 0.005 0.147
TUB cg25044765 Body 42.2 ± 3.5 45.3 ± 5.5 3.1 0.004 0.14
UBE2E3 cg13042464 Body 81.5 ± 2.2 82.9 ± 1.9 1.4 0.003 0.13
VEGFA cg00539360 TSS1500 34.2 ± 4.9 38.1 ± 7.0 3.9 0.003 0.13
cg18022921 TSS1500 28.9 ± 3.7 32.4 ± 6.1 3.5 0.003 0.13
WWOX cg07493562 Body 58.4 ± 4.3 53.4 ± 5.9 -5.0 0.00001 0.08
cg01630032 Body 79.8 ± 5.6 72.0 ± 12.2 -7.8 0.0001 0.08
cg08122051 Body 42.6 ± 5.2 48.4 ± 7.6 5.8 0.002 0.12
ZNF608 cg26878870 1stExon;5'UTR 43.4 ± 5.9 47.9 ± 5.6 4.5 0.001 0.11
cg22589697 Body 65.9 ± 3.0 67.9 ± 4.4 2.0 0.004 0.14
Table S16. CpG-sites that exhibit differential DNA methylation (q<0.15) in adipose tissue from 28 diabetic versus 28 non-diabetic subjects in parallel with an association between BMI and differential DNA methylation (p<0.05) in adipose tissue from 28 non-diabetic subjects. Excel-file
Table S17. CpG-sites that exhibit differential DNA methylation (q<0.15) in adipose tissue from 28 diabetic versus 28 non-diabetic subjects in parallel with an association between fasting glucose and differential DNA methylation (p<0.05) in adipose tissue from 28 non-diabetic subjects. Excel-file
Supplementary table 18. Correlation between mRNA expression and DNA methylation of the 197 genes with differential expression in adipose tissue from T2D discordant twins.
Negative correlation between DNA methylation and gene expression Positive correlation between DNA methylation and gene expression
CpG island CpG island Regr. Gene-related Gene Regr. Gene-related Gene Probe ID p value q value related Probe ID p value q value related coeff. region Name coeff. region region region
ACAT1 cg03920739 -0.28 0.004 0.08 TSS200 Island cg06648780 0.27 0.000003 0.001 Body
ACVR1C cg12698343 -0.19 0.003 0.07 TSS200 Island cg16654432 0.34 0.00001 0.003 Body
ASB1 cg13790879 -0.73 0.0004 0.02 Body Island cg04912993 0.27 0.0001 0.01 Body
ATPAF1 cg04138976 -0.86 0.003 0.07 TSS1500 S_Shore ALCAM cg15423944 0.19 0.003 0.07 Body
cg12807275 -0.87 0.00003 0.01 Body N_Shore cg09025274 0.27 0.003 0.08 Body
AVPR1A 1stExon; cg26706003 -0.66 0.0001 0.01 S_Shore cg24685239 0.24 0.01 0.11 Body 5'UTR
BCCIP cg26735793 -0.23 0.006 0.10 TSS1500 Island cg18412889 0.73 0.0003 0.02 Body N_Shore
cg00570269 -0.25 0.002 0.07 Body Island cg19933414 0.47 0.001 0.03 TSS1500 S_Shelf ALDH3B1 C13orf33 cg00367615 -0.35 0.003 0.08 Body Island cg25864978 0.69 0.002 0.07 Body N_Shelf
cg13251181 -0.25 0.003 0.08 Body S_Shore cg01408871 0.43 0.01 0.11 Body Island
C14orf39 cg12189551 -0.25 0.006 0.11 TSS200 Island ALDH6A1 cg11801651 0.25 0.001 0.03 TSS200 N_Shore
C9orf95 cg13845049 -0.47 0.005 0.09 Body;5'UTR N_Shore C11orf68 cg06954540 0.68 0.01 0.10 TSS200 Island cg26476820 -0.41 0.0000001 0.0001 TSS200 N_Shelf C1S cg21622186 0.34 0.0005 0.03 TSS1500
CAPG cg27139457 -0.42 0.0003 0.02 TSS200 N_Shelf cg20272205 0.65 0.000001 0.0005 TSS1500
cg07215695 -0.39 0.0003 0.02 TSS200 N_Shelf cg04132891 0.56 0.0001 0.01 Body
cg02081846 -0.39 0.0002 0.02 Body cg21307628 0.64 0.0001 0.01 TSS1500
CD44 5'UTR;1stEx cg14082886 -0.55 0.002 0.06 Body S_Shelf cg12113356 0.65 0.0001 0.01 on
CD68 cg05270696 -0.28 0.001 0.05 Body N_Shelf cg19593401 0.57 0.0002 0.02 TSS1500
5'UTR;1stEx CRB1 cg01258789 -1.12 0.002 0.06 TSS200 cg16198723 0.96 0.0004 0.02 CCDC80 on
5'UTR;1stEx CRBN cg18415483 -0.75 0.004 0.09 1stExon Island cg05963085 0.88 0.001 0.05 on
5'UTR;1stEx CSE1L cg19995112 -1.10 0.004 0.09 TSS1500 N_Shore cg02905245 1.03 0.001 0.05 on
1stExon;5'U cg17831791 -1.90 0.002 0.07 Body Island cg02954903 0.78 0.003 0.07 TR CTBP2 5'UTR;1stEx cg01213599 -1.02 0.010 0.15 Body cg13287247 0.61 0.01 0.10 on
cg16624891 -0.40 0.0001 0.01 5'UTR cg25868793 0.66 0.0003 0.02 Body CD276 CTSB cg21919729 -0.58 0.0001 0.01 5'UTR cg00117012 1.18 0.01 0.11 Body
cg08012294 -0.51 0.009 0.14 5'UTR N_Shore CD44 cg15695194 0.39 0.004 0.09 Body cg18563860 -0.94 0.00000003 0.00005 TSS1500 S_Shore cg14593191 0.54 0.005 0.09 Body
cg06125903 -1.12 0.00000004 0.00005 TSS1500 S_Shore cg15068132 1.72 0.00004 0.01 Body S_Shore CHPT1 cg04917472 -0.64 0.00005 0.01 TSS1500 S_Shore cg15340124 0.80 0.005 0.09 TSS200 Island
5'UTR;TSS2 cg00539174 -0.80 0.0001 0.01 TSS1500 S_Shore CLN3 cg09359817 0.41 0.01 0.14 Island 00;1stExon
cg13795831 -0.92 0.0001 0.01 TSS1500 S_Shore CRBN cg09463755 0.63 0.001 0.03 TSS200 Island
5'UTR;1stEx cg07464217 -0.48 0.0002 0.02 TSS1500 S_Shore CTBP2 cg12685995 1.65 0.01 0.14 Island on
CTSZ cg06942450 -0.55 0.001 0.04 TSS1500 S_Shore CTSB cg03654169 0.56 0.00001 0.003 Body
Body;1stExo cg20278790 -0.62 0.001 0.05 TSS1500 S_Shore cg21389309 0.41 0.0000001 0.0001 S_Shore n
cg22145559 -0.64 0.003 0.07 TSS1500 S_Shore cg20166931 0.23 0.0000002 0.0002 3'UTR S_Shore
cg17928895 -0.78 0.004 0.09 TSS1500 S_Shore cg08910550 0.22 0.000002 0.001 Body Island
cg02744249 -0.91 0.006 0.10 TSS1500 S_Shore cg22340526 0.14 0.00002 0.003 Body S_Shore DPP6 cg01623438 -0.82 0.006 0.11 TSS1500 S_Shore cg15770754 0.26 0.00002 0.004 Body Island
cg08545593 -0.90 0.008 0.14 TSS1500 S_Shore cg19470459 0.09 0.0001 0.01 3'UTR S_Shore
cg18245281 -0.79 0.009 0.15 TSS1500 S_Shore cg13345683 0.15 0.0003 0.02 Body S_Shore
CYP27A1 cg02930667 -0.60 0.002 0.07 Body cg18883476 0.24 0.0003 0.02 Body
DDB2 cg15500466 -0.45 0.0001 0.01 Body S_Shelf cg03472695 0.19 0.0004 0.02 Body cg14422827 -0.65 0.0002 0.02 Body S_Shore cg13725124 0.25 0.001 0.03 3'UTR S_Shore
cg00290086 -0.64 0.001 0.03 5'UTR N_Shore cg10860802 0.35 0.001 0.04 Body
DMRT2 cg14377594 -0.38 0.002 0.06 5'UTR N_Shore cg07915562 0.27 0.002 0.06 Body N_Shore
1stExon;5'U cg03740162 -0.30 0.007 0.11 N_Shore cg01620739 0.18 0.002 0.06 Body Island TR
DNA2 cg12416067 -0.14 0.009 0.15 1stExon Island cg11328677 0.22 0.002 0.07 Body N_Shore
cg13765278 -0.37 0.001 0.04 Body cg25042586 0.13 0.003 0.08 Body
cg16680167 -0.12 0.002 0.06 Body cg19162075 0.18 0.004 0.09 Body DPP6 cg27411746 -0.25 0.003 0.07 Body cg17370718 0.11 0.005 0.09 Body
cg17843376 -0.16 0.005 0.09 Body Island cg13989810 0.11 0.005 0.09 Body
EGR2 cg09011742 -0.53 0.002 0.06 5'UTR Island cg13123578 0.12 0.01 0.11 Body N_Shore
5'UTR;TSS2 EVC2 cg06426416 -1.03 0.001 0.05 Island cg11999800 0.20 0.01 0.13 Body N_Shore 00
TSS1500;TS cg15477144 -0.56 0.003 0.08 N_Shore FAM174A cg14575983 0.99 0.002 0.06 3'UTR S200 FAM118A TSS1500;TS cg12262698 -0.35 0.005 0.09 N_Shore FBXO4 cg10468059 0.42 0.0001 0.01 1stExon Island S200
FAM174A cg01306080 -0.54 0.001 0.04 TSS200 Island cg05373705 0.16 0.003 0.07 Body N_Shelf FCGBP FAM86B1 cg02230089 -0.66 0.001 0.05 Body N_Shelf cg24811685 0.13 0.004 0.09 Body N_Shore cg26796542 -0.68 0.002 0.06 TSS1500 S_Shore cg22031522 0.16 0.01 0.14 Body N_Shore
TSS200;TSS 5'UTR;1stEx cg18251245 -0.56 0.004 0.09 N_Shore cg09484039 0.34 0.0003 0.02 Island 1500 on FBXO34 FRZB 5'UTR;TSS2 cg15990800 -0.56 0.009 0.14 Island cg01481989 0.26 0.003 0.07 1stExon Island 00
GABRB2 cg01101742 -0.13 0.003 0.07 5'UTR N_Shore FXYD5 cg12055183 0.42 0.002 0.07 Body S_Shelf
TSS200;TSS cg08468689 -1.17 0.000004 0.001 GPNMB cg03113800 0.22 0.002 0.06 Body 1500
GHDC TSS200;5'U cg17050693 -0.66 0.001 0.05 cg16044595 0.51 0.001 0.04 TSS1500 N_Shore TR;1stExon
cg13053608 -0.72 0.006 0.10 5'UTR;Body GPR137B cg19249231 0.45 0.003 0.07 TSS1500 N_Shore
GPT2 cg05380921 -0.33 0.002 0.06 Body;5'UTR S_Shelf cg23655242 0.18 0.003 0.08 Body
HIST1H3B cg10075390 -0.23 0.0002 0.02 1stExon Island cg23646820 0.37 0.01 0.11 TSS1500 N_Shore
HM13 cg17840843 -0.23 0.001 0.05 Body Island cg13647528 0.76 0.00003 0.01 TSS200
HOMER3 cg02774856 -0.84 0.002 0.06 TSS1500 S_Shore cg08335254 1.21 0.0002 0.02 Body
HPS3 cg22697692 -0.69 0.0005 0.03 Body S_Shelf GRAMD1 cg03627771 0.71 0.0005 0.03 TSS1500
IMMP1L cg04972224 -0.28 0.001 0.05 5'UTR N_Shore B cg14374432 1.06 0.001 0.03 TSS200
KIAA0922 cg24020152 -0.71 0.0001 0.01 Body cg05889171 1.12 0.001 0.03 Body S_Shore
KIAA0922 cg21908828 -0.47 0.001 0.03 TSS1500 N_Shore cg06174296 0.53 0.001 0.04 1stExon;5'U TR
cg20367304 -0.34 0.002 0.06 Body S_Shelf cg18771577 0.80 0.001 0.05 Body S_Shelf
cg01927162 -0.81 0.008 0.13 Body cg01699740 0.71 0.002 0.06 TSS200
LDB2 cg05074133 -0.72 0.010 0.15 Body cg15268963 0.65 0.002 0.07 Body
LYPLAL1 cg19753174 -0.76 0.00002 0.004 Body S_Shelf cg05543458 1.04 0.004 0.08 Body
MAP1B cg17776376 -0.33 0.002 0.07 Body cg16699198 0.68 0.005 0.09 Body
MYOF cg14428166 -0.97 0.000001 0.001 Body cg26393964 0.66 0.005 0.09 TSS1500
cg27107893 -1.37 0.0002 0.02 Body cg26041232 0.47 0.01 0.10 Body Island
cg18998365 -1.10 0.0003 0.02 5'UTR N_Shore cg13247967 0.62 0.01 0.14 Body
cg17342132 -1.21 0.001 0.05 Body N_Shore HIBCH cg17377164 0.46 0.000001 0.001 TSS200 Island NR3C1 5'UTR;TSS1 cg14558428 -0.49 0.003 0.07 Island HM13 cg20129782 0.61 0.01 0.10 Body S_Shore 500
cg06613263 -1.25 0.003 0.08 Body N_Shelf HOMER3 cg08894891 0.60 0.0003 0.02 Body Island
TSS1500;TS PAIP2 cg00955682 -1.02 0.006 0.10 Island HS3ST2 cg04687409 0.31 0.001 0.05 Body S200
PAIP2B cg06241044 -0.42 0.0001 0.01 5'UTR N_Shelf ISLR cg15480336 0.56 0.01 0.15 TSS1500 N_Shelf
cg00702008 -0.15 0.001 0.04 TSS1500 Island cg22776386 0.97 0.00003 0.01 Body PCLO ITIH5 cg13909585 -0.11 0.005 0.10 TSS200 Island cg00455523 0.72 0.00004 0.01 Body;3'UTR PDS5A cg14009745 -0.99 0.002 0.06 5'UTR;Body Island cg17753476 0.49 0.0001 0.01 Body Island
cg12433486 -1.06 0.00000002 0.00005 5'UTR N_Shore cg20023675 0.44 0.003 0.07 Body Island PKM2 cg24327132 -0.83 0.001 0.05 5'UTR N_Shore cg06201219 0.64 0.003 0.08 3'UTR
5'UTR;1stEx PLD3 cg08388939 -0.48 0.001 0.04 Island cg12067981 0.69 0.004 0.09 Body Island on
RAB13 cg00205485 -0.61 0.004 0.09 TSS200 cg09759523 0.70 0.01 0.10 Body Island
RB1 cg02113449 -0.43 0.009 0.14 TSS1500 Island cg09955886 0.67 0.01 0.12 3'UTR
RNF125 cg16929139 -0.51 0.005 0.09 Body S_Shelf KCTD7 cg15423613 0.46 0.005 0.09 TSS1500 Island
cg26894575 -0.21 0.001 0.03 5'UTR cg25570522 0.21 0.004 0.08 Body KIAA0922 S100A4 cg18273417 -0.45 0.001 0.03 TSS200 cg26055899 0.29 0.004 0.09 Body
cg13091627 -0.20 0.006 0.10 TSS200 KRCC1 cg08305742 0.59 0.001 0.03 5'UTR Island
cg26674160 -0.36 0.0001 0.01 TSS200 LGALS9C cg18522239 0.32 0.005 0.09 3'UTR
S100B LOC44120 cg11064537 -0.43 0.0004 0.02 5'UTR cg13757081 0.55 0.004 0.08 Body 4
SHOC2 cg19176816 -1.50 0.001 0.05 TSS200 Island cg12001709 1.03 0.01 0.10 Body S_Shore MICB SNHG12 cg17459893 -0.51 0.002 0.07 TSS200 Island cg07315969 0.67 0.01 0.11 Body
cg12738913 -0.72 0.0004 0.02 Body S_Shelf cg08869118 0.54 0.0001 0.01 Body SNTG2 MLXIP cg17600393 -0.70 0.003 0.08 Body N_Shore cg04739485 0.93 0.0001 0.01 Body cg05299774 -0.54 0.005 0.09 Body cg26166956 0.58 0.002 0.05 Body
ST14 cg09586924 -0.37 0.001 0.05 Body S_Shelf cg07241154 0.34 0.002 0.06 Body Island
cg13848707 -0.47 0.004 0.08 5'UTR S_Shore cg22501243 0.52 0.003 0.07 Body TET1 cg12630147 -0.39 0.007 0.12 5'UTR S_Shore cg06216468 0.51 0.01 0.15 3'UTR
TTLL7 cg03959147 -0.70 0.0003 0.02 5'UTR MYL9 cg19214331 0.67 0.003 0.08 TSS1500 Island
ZNF92 cg08326497 -0.38 0.004 0.08 TSS1500 N_Shore cg04887082 0.39 0.0003 0.02 Body
cg16358099 0.58 0.0005 0.03 Body MYOF cg10435454 0.59 0.01 0.10 Body
cg12085226 0.63 0.01 0.13 Body
NR3C1 cg16586394 0.96 0.002 0.06 Body
5'UTR;1stEx PAIP2 cg25124965 0.97 0.004 0.08 Island on
PCLO cg07321237 0.17 0.004 0.08 Body
PDS5A cg17542806 2.14 0.01 0.11 Body
cg10401733 0.47 0.001 0.03 3'UTR S_Shore PKM2 cg23893460 0.37 0.01 0.13 Body S_Shelf
cg15439221 0.80 0.00001 0.003 3'UTR PLBD2 cg02760555 0.52 0.001 0.03 3'UTR cg16381917 0.58 0.01 0.11 Body S_Shore
cg16700466 0.44 0.002 0.06 3'UTR N_Shelf PLD3 cg00456774 0.33 0.002 0.06 5'UTR S_Shelf
PLXNA1 cg23526071 0.57 0.003 0.08 Body S_Shore
cg04560534 0.48 0.0002 0.02 Body PPT1 cg24788636 0.22 0.004 0.08 Body Island
PSAP cg26960370 1.17 0.00001 0.002 3'UTR
cg25676335 0.92 0.0001 0.01 Body S_Shore
cg00059930 1.11 0.0002 0.02 Body S_Shore
cg19254235 1.42 0.001 0.03 Body S_Shore
cg26119796 1.49 0.001 0.04 Body S_Shore RB1 cg18481241 0.97 0.001 0.04 Body Island
cg03085377 0.72 0.002 0.06 Body Island
cg19427472 0.80 0.002 0.06 Body Island
cg26740195 0.87 0.003 0.07 Body S_Shore
SCYL2 cg22425355 0.55 0.005 0.09 TSS1500 Island
SEMA3G cg25134747 0.67 0.01 0.10 TSS1500
SERPING1 cg14691871 0.48 0.003 0.07 3'UTR cg12783776 0.81 0.004 0.08 Body
SHOC2 cg21022395 1.17 0.01 0.14 5'UTR
SLC36A1 cg04550063 0.50 0.002 0.06 TSS200 N_Shore
cg23894948 0.33 0.0003 0.02 TSS1500 S_Shore SLC7A4 cg04054731 0.18 0.005 0.09 5'UTR Island
cg03098782 0.38 0.002 0.06 Body ST14 cg14830082 0.33 0.01 0.11 Body
1stExon;5'U STARD3 cg09642357 0.64 0.002 0.05 Island TR
STK32B cg14582191 0.47 0.005 0.09 Body
TNFSF12- cg08090557 1.12 0.004 0.08 Body N_Shore
TNFSF13 cg12045829 1.72 0.01 0.12 Body S_Shore
cg18028767 0.69 0.002 0.05 5'UTR;Body S_Shore
cg23938637 1.28 0.002 0.06 Body
TSPAN4 cg20171011 1.11 0.004 0.09 Body
cg20676047 0.87 0.004 0.09 5'UTR;Body N_Shore
cg22749642 0.98 0.01 0.12 5'UTR;Body N_Shore
ZNF613 cg00008033 0.55 0.001 0.05 TSS1500 ZNF655 cg05165378 1.10 0.000001 0.0004 TSS1500 N_Shore
ZNF92 cg14090510 0.51 0.004 0.08 5'UTR;Body Island
Supplementary table 19. Correlation between mRNA expression and DNA methylation of the 20 genes with largest expression differences in adipose tissue from T2D discordant twins.
Negative correlation between DNA methylation and gene expression Positive correlation between DNA methylation and gene expression
CpG Gene- Regr. q Gene-related island Gene Regr. q CpG island Gene Probe ID p value Probe ID p value related coeff. value region related Name coeff. value related region region region
C12orf39 cg24957964 -0.03 0.01 0.15 TSS1500 N_Shelf FADS2 cg14911132 0.12 0.002 0.07 Body S_Shore
1stExon; ELOVL6 cg03460315 -0.12 0.0002 0.01 Body cg17669033 0.11 0.003 0.08 IL1RN 5'UTR
cg10515671 -0.18 0.000008 0.002 TSS1500 S_Shore cg06658391 0.13 0.009 0.14 TSS1500 FADS1 cg07689907 -0.10 0.001 0.05 Body Island MMP9 cg15876464 0.29 0.005 0.10 Body Island
5'UTR; TSS1500; cg04184278 -0.15 0.00009 0.006 cg03700944 0.09 0.0001 0.01 S_Shore 1stExon TSS200 GYS2 PLA2G7 TSS200; cg06141025 -0.09 0.005 0.10 1stExon cg04851935 0.09 0.006 0.10 Island 5'UTR
MSR1 cg16303562 -0.12 0.005 0.10 TSS200 SPP1 cg00583003 0.07 0.006 0.11 TSS1500
cg22496559 -0.21 0.00009 0.006 TSS200
TM4SF19 cg13314965 -0.11 0.0003 0.01 TSS1500
cg13605674 -0.10 0.002 0.05 TSS200 cg21090033 -0.15 0.005 0.10 TSS200 cg01883662 -0.07 0.008 0.13 TSS200 cg11363229 -0.11 0.009 0.13 TSS200
Supplementary table 20. Correlation between mRNA expression and DNA methylation of the 33 T2D and obesity candidate genes with expression differences in adipose tissue from T2D discordant twins.
Negative correlation between DNA methylation and gene expression Positive correlation between DNA methylation and gene expression
CpG CpG Gene- Gene- Regr. island Gene Regr. island Gene Probe ID p value q value related Probe ID p value q value related coeff. related Name coeff. related region region region region
CADM2 cg18458597 -0.33 0.002 0.09 Body ETV5 cg04400533 0.36 0.001 0.05 Body Island
0.0000 TSS1500; cg03322057 -0.75 0.0003 0.03 Body cg10984625 0.47 0.01 3 Body
cg26020878 -0.56 0.002 0.07 Body cg02970663 0.70 0.0001 0.01 Body
cg02338271 -0.56 0.002 0.08 Body cg05491478 0.21 0.0001 0.02 Body DNM3 3'UTR; cg02633729 -0.87 0.003 0.11 Body cg05172609 0.67 0.0001 0.02 Body LRRFIP1 cg24002149 -0.96 0.004 0.11 Body cg15674813 0.33 0.0005 0.04 Body
cg23391785 -0.35 0.005 0.12 Body Island cg02970663 0.62 0.0005 0.04 Body
0.000000 0.0000 cg13804450 -0.66 Body cg24656153 0.75 0.0005 0.04 TSS200 GLIS3 0001 002
cg14110111 -0.35 0.002 0.08 5'UTR N_Shore cg05491478 0.27 0.001 0.04 Body Island
LRP1B cg03252605 -0.13 0.0003 0.04 Body cg02970663 0.49 0.001 0.07 Body cg21340845 -0.11 0.001 0.04 TSS1500 S_Shelf cg19239304 0.53 0.001 0.07 Body S_Shore
cg09174717 -0.17 0.001 0.06 Body cg07063912 0.83 0.002 0.08 Body
3'UTR; cg05686197 -0.18 0.003 0.11 Body cg05172609 0.33 0.002 0.08 Body
TSS1500; cg20218460 -0.68 0.001 0.05 Body cg10984625 0.43 0.003 0.11 Body
TSS1500; cg15261462 -0.52 0.001 0.06 Body cg09037813 0.26 0.004 0.12 Body
LRRFIP1 TSS1500; cg09037813 -0.75 0.002 0.07 N_Shore cg12302119 0.47 0.0002 0.03 Body Body NEGR1
cg07558690 -1.04 0.002 0.08 Body cg03548170 0.66 0.004 0.11 Body N_Shelf
TSS1500; cg10984625 -0.80 0.004 0.11 Island NUDT3 cg16767886 1.10 0.001 0.05 Body N_Shore Body
LYPLAL1 cg19753174 -0.76 0.00002 0.01 Body S_Shelf cg11348994 0.59 0.001 0.05 TSS1500 Island PCSK1 NCAM2 cg19556343 -0.48 0.001 0.05 TSS1500 Island cg17803175 0.62 0.002 0.08 TSS200
5'UTR; cg25929976 -0.72 0.001 0.05 TSS1500 N_Shore cg26786980 0.31 0.0003 0.03 Island RARB 1stExon PPARG cg10499651 -0.75 0.003 0.09 Body cg27574595 0.23 0.001 0.07 Body N_Shelf
cg16827534 -1.17 0.003 0.09 5'UTR S_Shelf cg04270652 0.33 0.002 0.08 TSS1500 SULT1A2 RARB cg02746691 -0.20 0.002 0.08 Body cg01621080 0.32 0.004 0.11 5'UTR;TS N_Shore S1500
5'UTR;TS cg03531687 -0.24 0.003 0.09 3'UTR cg00931491 0.28 0.005 0.14 N_Shelf S1500
cg23400797 -0.73 0.0005 0.04 TSS200 S_Shore RBMS1 cg23400797 -0.68 0.004 0.11 TSS200 S_Shore
cg00005040 -0.15 0.000002 0.001 TSS1500 N_Shore
cg00752628 -0.10 0.00004 0.01 Body N_Shore
cg24470447 -0.15 0.0001 0.02 Body S_Shore
RSPO3 1stExon;5 cg09979256 -0.09 0.0004 0.04 Island 'UTR
cg10997634 -0.20 0.001 0.05 3'UTR
cg03778155 -0.10 0.001 0.07 Body Island
0.000000 cg25373579 -0.56 0.0002 3'UTR 3
cg00539360 -0.65 0.00004 0.01 TSS1500 N_Shore
VEGFA cg18022921 -0.64 0.0002 0.03 TSS1500 N_Shore
cg01298514 -0.61 0.003 0.09 TSS1500 N_Shore
cg21099624 -0.25 0.003 0.11 TSS200 Island
cg23879496 -0.28 0.004 0.11 Body cg12279019 -0.62 0.005 0.14 Body S_Shore
Supplementary table 21. Differential expression of genes in adipose tissue from the discordant twins that may contribute to regulation of DNA methylation.
Non-T2D T2D Difference Gene symbol Gene description Probe ID p value q value mean ± SD mean ± SD (%)
TET1 tet methylcytosine dioxygenase 1 7927876 210.0 ± 24.7 177.6 ± 32.4 -15.4 0.001 0.14
FOLR2 folate receptor 2 (fetal) 7942372 532.0 ± 270.5 822.2 ± 285.3 54.5 0.002 0.17
FOLR3 folate receptor 3 (gamma) 7942328 109.9 ± 7.4 121.1 ± 14.5 10.2 0.005 0.19
methylenetetrahydrofolate dehydrogenase MTHFD1 7975045 701.6 ± 131.6 609.1 ± 111.0 -13.2 0.005 0.19 (NADP+ dependent) 1
methylenetetrahydrofolate dehydrogenase MTHFD1L 8161484 2256.0 ± 395.7 1933.2 ± 336.0 -14.3 0.005 0.19 (NADP+ dependent) 1-like
methylenetetrahydrofolate dehydrogenase MTHFD2L 8095705 67.3 ± 7.6 60.3 ± 5.4 -10.4 0.01 0.21 (NADP+ dependent) 2-like
methylenetetrahydrofolate dehydrogenase MTHFD1L 8155563 2229.3 ± 371.4 1934.9 ± 340.7 -13.2 0.01 0.22 (NADP+ dependent) 1-like
solute carrier family 46 (folate transporter), SLC46A1 8013616 217.3 ± 34.5 252.8 ± 37.9 16.3 0.01 0.22 member 1
DNMT1 DNA (cytosine-5-)-methyltransferase 1 8033912 301.4 ± 25.7 321.5 ± 17.4 6.7 0.02 0.27 methylenetetrahydrofolate dehydrogenase MTHFD1L 8155630 2547.1 ± 492.5 2186.0 ± 382.3 -14.2 0.02 0.27 (NADP+ dependent) 1-like
FOLH1B folate hydrolase 1B 7942998 18.1 ± 2.0 16.8 ± 1.9 -7.2 0.03 0.32
DHFR dihydrofolate reductase 8022640 577.2 ± 165.5 477.1 ± 86.5 -17.3 0.04 0.35
Figure S1. Technical validation. Spearman correlations between results obtained with quantitative real-time PCR (x-axis) and array data (y-axis) for ELOVL6 mRNA expression (A), GYS2 mRNA expression (B), FADS1 mRNA expression (C), SPP1 (OPN) mRNA expression (D), CCL18 mRNA expression (E) and IL1RN mRNA expression (F). A.u.; arbitrary units.
A B
ELOVL6 GYS2 1500 800
600 1000 rho=0.76 400 rho=0.90 500 p=1.7x10-5 p=3.4x10-9 200
0 0 Quantity array (a.u.) array Quantity 0 10 20 30 40 50 (a.u.) array Quantity 0 2 4 6 8 10 Quantity real-time PCR (a.u.) Quantity real-time PCR (a.u.)
C D FADS1 SPP1 (OPN) 2500 2500
2000 2000
1500 1500 rho=0.87 rho=0.97 1000 1000 p=3.1x10-8 p=1.7x10-14 500 500
0 0 Quantity array (a.u.) array Quantity 0 5 10 15 20 25 (a.u.) array Quantity 0 2 4 6 8 10 Quantity real-time PCR (a.u.) Quantity real-time PCR (a.u.)
E F CCL18 IL1RN 800 500
400 600 300 400 rho=0.91 200 rho=0.96 200 -13 p=6.3x10-10 100 p=2.1x10
0 0 Quantity array (a.u.) array Quantity 0 2 4 6 (a.u.) array Quantity 0 1 2 3 4 5 Quantity real-time PCR (a.u.) Quantity real-time PCR (a.u.)
Figure S2. Replication of methylation data. The two CpG-sites with methylation differences >3% in adipose tissue of five twin pairs discordant for T2D identified by Ribel- Madsen et al (PlosOne 2012) were also differentially methylated in discordant twins in our study. Data are mean ± SD. * p<0.05.
80 Non-diabetic * T2D 60 * 40
20
DNA methylation (%) methylation DNA 0 SFT2D3 C8orf31 cg11206634 cg04612566