TABLE 2.
Summary statistics for association of age of onset of T2D for 25 independent single-nucleotide polymorphisms in Caucasians study participants from ADVANCE. Genome-wide association studies were done for all study participants (n = 3409 combined group) and separately for Celtic (n = 2307) and Slavic (n = 1102) individuals stratified by ethnic origin, which is determined by principal component analysis. Selected single-nucleotide polymorphisms for all groups are associated to age at diagnosis of diabetes with P value less than 1 × 10−5
| Celtic | Slavic | Combinedc | |||||||||||
| SNP ID | Chr | Position (bp, hg19) | RA | Locusa | P value | RAF% | Effect sizeb | P value | RAF% | Effect sizeb | P value | RAF% | Effect sizeb |
| SNPs that are significantly associated in both Celtic and Slavic genetic profiles and that increase in significance in combined groupc | |||||||||||||
| rs34428389 | 3 | 52 894 142 | A | TMEM110, MIR8064, SFMBT1 | 3.3 × 10−4 | 19.1 | −2.00 | 8.9 × 10−3 | 18.4 | −1.43 | 8.1 × 10−6 | 18.9 | −2.47 |
| rs17447640 | 4 | 42 555 811 | G | ATP8A1, SHISA3, GRXCR1 | 1.1 × 10−5 | 13.9 | −2.15 | 5.6 × 10−2 | 15.7 | −0.98 | 1.5 × 10−6 | 14.5 | −2.39 |
| rs11298745 | 7 | 18 548 252 | Del | HDAC9, MIR1302–6, TWIST1 | 2.3 × 10−3 | 90.5 | −1.26 | 4.6 × 10−5 | 90.0 | −1.73 | 1.6 × 10−6 | 90.3 | −2.01 |
| rs34620785 | 8 | 103 452 308 | A | UBR5, ODF1 | 1.6 × 10−4 | 88.4 | −1.71 | 1.7 × 10−3 | 84.4 | −1.61 | 1.6 × 10−6 | 87.1 | −2.27 |
| rs76703216 | 10 | 9 512 026 | G | LOC101928272 | 3.8 × 10−5 | 94.1 | −1.37 | 3.5 × 10−2 | 96.2 | −0.57 | 3.6 × 10−6 | 94.7 | −1.46 |
| rs35372009 | 14 | 38 782 341 | Del | CLEC14A, LINC00639 | 1.1 × 10−2 | 42.5 | −1.78 | 9.0 × 10−6 | 39.5 | −3.07 | 3.3 × 10−6 | 41.6 | −3.24 |
| rs148077446 | 16 | 77 310 608 | Del | SYCE1L, ADAMTS18 | 1.6 × 10−4 | 28.7 | −2.42 | 5.0 × 10−3 | 31.9 | −1.85 | 5.7 × 10−6 | 29.7 | −2.93 |
| SNPs that are only significantly associated in Celtic profile | RAF% | AF% | AF% | ||||||||||
| rs12743974 | 1 | 67 708 357 | A | IL23R, C1ORF141, IL12RB2 | 5.3 × 10−6 | 41.9 | −3.18 | 3.8 × 10−1 | 41.8 | 0.62 | 1.2 × 10−3 | 41.8 | −2.25 |
| rs12736701 | 1 | 77 815 425 | C | AK5, PIGK, ZZZ3 | 7.6 × 10−6 | 93.4 | −1.57 | 8.4 × 10−1 | 93.9 | 0.07 | 3.2 × 10−4 | 93.6 | −1.24 |
| rs7412314 | 1 | 171 287 252 | T | FMO4, FMO1, TOP1P1 | 4.3 × 10−6 | 73.3 | −2.88 | 6.5 × 10−1 | 69.8 | −0.30 | 6.3 × 10−5 | 72.1 | −2.53 |
| rs11099942 | 4 | 155 132 707 | T | SFRP2, DCHS2 | 4.3 × 10−6 | 6.4 | −1.59 | 6.7 × 10−1 | 5.1 | 0.13 | 1.7 × 10−4 | 5.9 | −1.26 |
| rs9502478 | 6 | 6 593 695 | T | LY86-AS1, F13A1 | 4.3 × 10−6 | 17.3 | −2.46 | 6.3 × 10−1 | 16.0 | −0.25 | 3.2 × 10−5 | 16.9 | −2.20 |
| rs2107167 | 7 | 109 590 911 | A | EIF3IP1 | 8.0 × 10−6 | 13.7 | −2.17 | 9.6 × 10−1 | 9.6 | −0.02 | 4.1 × 10−5 | 12.4 | −1.91 |
| rs10973627 | 9 | 37 971 389 | C | SHB, SLC25A51, ALDH1B1 | 4.1 × 10−6 | 87.7 | −2.14 | 6.4 × 10−1 | 89.2 | −0.21 | 9.9 × 10−6 | 88.2 | −2.02 |
| rs113932007 | 11 | 115 491 436 | Del | CADM1, LINC00900 | 5.9 × 10−7 | 65.1 | −3.37 | 5.1 × 10−1 | 64.5 | −0.45 | 8.8 × 10−6 | 64.9 | −3.00 |
| rs10512488 | 17 | 40 963 904 | G | BECN1, CNTD1, MIR6781 | 3.1 × 10−6 | 74.0 | −2.90 | 2.9 × 10−1 | 72.2 | −0.67 | 9.5 × 10−6 | 73.4 | −2.77 |
| SNPs that are only significantly associated in Slavic profile | AF% | RAF% | AF% | ||||||||||
| rs340841 | 1 | 214 124 470 | C | PROX1-AS1, LINC00538, PROX1 | 7.9 × 10−1 | 45.9 | 0.19 | 8.6 × 10−6 | 52.8 | −3.14 | 2.5 × 102 | 48.1 | −1.59 |
| rs12714314 | 2 | 1 943 617 | C | MYT1L, PXDN, MYT1L-AS1 | 9.3 × 10−1 | 75.8 | 0.05 | 3.4 × 10−6 | 72.8 | −2.92 | 1.9 × 10−2 | 74.9 | −1.44 |
| rs58383906 | 3 | 29 246 181 | C | LINC00693, RBMS3-AS3 | 3.3 × 10−1 | 51.5 | −0.68 | 2.8 × 10−6 | 50.3 | −3.32 | 6.9 × 10−4 | 51.1 | −2.40 |
| rs13166103 | 5 | 57 742 202 | C | LOC101928569, PLK2 | 3.5 × 10−1 | 81.3 | 0.51 | 4.1 × 10−6 | 79.8 | −2.61 | 9.4 × 10−2 | 80.8 | −0.93 |
| rs12188216 | 5 | 166 425 736 | G | CTB-7E3.1, TENM2 | 2.9 × 10−1 | 10.7 | −0.46 | 9.7 × 10−6 | 9.7 | −1.85 | 1.7 × 10−3 | 10.3 | −1.35 |
| rs9384193 | 6 | 154 554 249 | C | OPRM1, CNKSR3 | 8.7 × 10−1 | 36.3 | 0.11 | 8.8 × 10−6 | 36.3 | −3.02 | 2.7 × 10−2 | 36.3 | −1.50 |
| rs11060464 | 12 | 130 097 850 | G | TMEM132D, LOC101927735, LOC100190940 | 5.4 × 10−1 | 70.9 | 0.39 | 3.7 × 10−6 | 73.1 | −2.90 | 6.0 × 10−2 | 71.6 | −1.20 |
| rs1754680 | 14 | 38 848 003 | A | CLEC14A, LINC00639 | 2.3 × 10−2 | 59.4 | −1.54 | 8.3 × 10−6 | 57.4 | −3.17 | 4.8 × 10−5 | 58.7 | −2.85 |
| rs13043901 | 20 | 52 170 783 | A | LOC101927770, TSHZ2, ZNF217 | 3.3 × 10−1 | 75.3 | −0.60 | 5.0 × 10−6 | 76.5 | −2.74 | 4.2 × 10−4 | 75.7 | −2.14 |
RA, risk allele; RAF, risk allele frequency; SNP, single-nucleotide polymorphism.
aIf gene is in bold, SNP lies within the gene.
bThe effect size (ES) is determined by the β, MAF, and standard error using the equation described in literature [37].
cAssociation is considered replicated in two independent samples when P values are nominally significant for each of Celtic and Slavic samples and are more significant for combined sample.