Table 1.
Results for the 20 SNPs taken forward into stage 2 that reached P < 5 × 10−7 in joint analyses
| SNP | Candidate gene | Chromosome (position) |
Alleles (1/2) |
MAF | Additive model test P |
Gender test P |
Male s.d. difference (95% CI) |
Female s.d. difference (95% CI) |
R2 (%) |
GWA study P |
Follow-up P | Heterogeneity P |
Overall P excluding DGI |
Overall P |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| rs6440003 | ZBTB38 | 3 (142576907) | A/G | 0.44 | 0.80 | 0.01 | 0.07 (0.04, 0.09) |
0.12 (0.09, 0.14) |
0.32 | 1.3 × 10−14 | 8.7 × 10−12 | 0.52 | 2.7 × 10−23 | 1.8 × 10−24 |
| rs2282978/ rs42046a |
CDK6 | 7 (91898623) | C/T | 0.33 | 0.14 | 0.69 | 0.09 (0.06, 0.12) |
0.08 (0.05, 0.11) |
0.28 | 5.0 × 10−11 | 5.1 × 10−13 | 0.98 | 3.1 × 10−21 | 7.8 × 10−23 |
| rs1042725 | HMGA2 | 12 (64644614) | C/T | 0.49 | 0.70 | 0.34 | 0.05 (0.03, 0.08) |
0.07 (0.05, 0.10) |
0.25 | 5.9 × 10−9 | 8.6 × 10−11 | 0.50 | 1.1 × 10−14 | 2.5 × 10−18 |
| rs6060373 | GDF5 | 20 (33377622) | A/G | 0.38 | 0.17 | 0.70 | -0.08 (-0.11, -0.05) |
-0.07 (-0.10, -0.04) |
0.21 | 2.2 × 10−12 | 1.6 × 10−7 | 0.27 | 2.0 × 10−15 | 1.7 × 10−17 |
| rs16896068 | LCORL | 4 (17621109) | A/G | 0.16 | 0.31 | 0.99 | -0.07 (-0.11, -0.03) |
-0.07 (-0.11, -0.03) |
0.12 | 1.0 × 10−4 | 2.5 × 10−10 | 0.06 | 2.0 × 10−13 | 2.4 × 10−13 |
| rs4549631 | LOC387103 | 6 (127008001) | C/T | 0.50 | 0.62 | 0.85 | 0.06 (0.03, 0.08) |
0.05 (0.03, 0.08) |
0.11 | 1.2 × 10−8 | 4.6 × 10−6 | 0.47 | 2.9 × 10−11 | 4.7 × 10−13 |
| rs3791675 | EFEMP1 | 2 (56022960) | C/T | 0.23 | 0.43 | 0.34 | 0.09 (0.05, 0.12) |
0.06 (0.03, 0.10) |
0.12 | 7.1 × 10−8 | 6.0 × 10−6 | 0.54 | 1.5 × 10−12 | 2.2 × 10−12 |
| rs2814993 | C6orf106 | 6 (34726871) | A/G | 0.15 | 0.18 | 0.87 | 0.09 (0.05, 0.13) |
0.10 (0.06, 0.14) |
0.20 | 8.9 × 10−9 | 5.7 × 10−5 | 0.04 | 4.0 × 10−11 | 4.1 × 10−12 |
| rs10512248 | PTCH1 | 9 (95339258) | G/T | 0.31 | 0.14 | 0.10 | 0.05 (0.02, 0.07) |
0.08 (0.05, 0.11) |
0.19 | 1.5 × 10−6 | 6.0 × 10−6 | 0.82 | 1.0 × 10−9 | 4.2 × 10−11 |
| rs12735613 | SPAG17 | 1 (118596015) | A/G | 0.24 | 0.0090 | 0.02 | -0.08 (-0.11, -0.05) |
-0.03 (-0.06, 0.00) |
0.09 | 3.4 × 10−8 | 8.2 × 10−5 | 0.51 | 2.0 × 10−9 | 4.4 × 10−11 |
| rs11107116 | SOCS2 | 12 (92480972) | G/T | 0.23 | 0.047 | 0.73 | -0.04 (-0.07, -0.01) |
-0.05 (-0.08, -0.02) |
0.06 | 2.5 × 10−5 | 5.6 × 10−6 | 0.41 | 2.3 × 10−8 | 5.6 × 10−10 |
| rs6854783/ rs2055059a |
HHIP | 4 (146000684) | A/G | 0.43 | 0.17 | 0.50 | 0.06 (0.03, 0.08) |
0.04 (0.01, 0.017) |
0.10 | 1.2 × 10−5 | 3.2 × 10−5 | 0.24 | 2.2 × 10−8 | 2.1 × 10−9 |
| rs1390401 | ZNF678 | 1 (224104685) | A/G | 0.18 | 0.0067 | 0.34 | 0.04 (0.01, 0.08) |
0.07 (0.03, 0.10) |
0.09 | 4.3 × 10−6 | 2.0 × 10−4 | 0.58 | 1.4 × 10−6 | 5.4 × 10−9 |
| rs3116602 | DLEU7 | 13 (50009356) | G/T | 0.21 | 0.88 | 0.02 | -0.04 (-0.07, 0.00) |
-0.09 (-0.12, -0.06) |
0.07 | 5.6 × 10−6 | 1.8 × 10−4 | 0.82 | 6.1 × 10−9 | 6.8 × 10−9 |
| rs6686842 | SCMH1 | 1 (41199964) | C/T | 0.44 | 0.30 | 0.97 | -0.05 (-0.08, -0.02) |
-0.05 (-0.08, -0.02) |
0.14 | 8.6 × 10−6 | 3.3 × 10−4 | 0.57 | 4.9 × 10−7 | 1.7 × 10−8 |
| rs10906982 | ADAMTSL3 | 15 (82371586) | A/T | 0.48 | 0.33 | 0.92 | 0.05 (0.02, 0.07) |
0.04 (0.02, 0.07) |
0.07 | 5.4 × 10−7 | 2.1 × 10−3 | 0.57 | 5.3 × 10−7 | 1.7 × 10−8 |
| rs6724465 | IHH | 2 (219769351) | A/G | 0.10 | 0.96 | 0.85 | -0.06 (-0.10, -0.02) |
-0.05 (-0.10, -0.01) |
0.04 | 3.1 × 10−5 | 2.8 × 10−4 | 0.52 | 2.2 × 10−6 | 2.1 × 10−8 |
| rs10935120 |
ANAPC13 or CEP63 |
3 (135715790) | A/G | 0.33 | 0.10 | 0.63 | -0.06 (-0.09, -0.03) |
-0.05 (-0.08, -0.02) |
0.10 | 2.2 × 10−6 | 3.1 × 10−3 | 0.57 | 8.7 × 10−7 | 7.3 × 10−8 |
| rs8041863 | ACAN | 15 (87160693) | A/T | 0.47 | 0.90 | 0.21 | 0.04 (0.01, 0.06) |
0.06 (0.03, 0.09) |
0.03 | 2.2 × 10−5 | 8.6 × 10−4 | 0.02 | 4.9 × 10−9 | 8.1 × 10−8 |
| rs8099594 | DYM | 18 (45245158) | A/G | 0.35 | 0.69 | 0.53 | 0.05 (0.02, 0.08) |
0.04 (0.01, 0.07) |
0.01 | 7.8 × 10−6 | 4.1 × 10−3 | 0.008 | 1.6 × 10−8 | 3.1 × 10−7 |
The results are ordered by the joint-analyses P value. Chromosome positions are based on NCBI build 125. The alleles all refer to the positive strand. Betas are per each additional copy of allele 1. Minor allele frequency (MAF) based on the minor allele (bold and underlined in the alleles column) in the WTCCC-T2D study. R2 (% variation explained) is for follow-up sample only and does not include CoLaus. The additive model test and gender test P values do not include data from DGI or CoLaus.
r2 = 1 proxies used in the stage 2 studies because of assay design issues. Candidate gene is given when monogenic human and/or mouse phenotypes and/or expression results clearly implicate a gene. An overall P value excluding DGI is given because of the small related component of DGI and to provide evidence independent from the accompanying manuscript by Lettre et al.18