TABLE 3.
BMI-stratified analyses for other confirmed type 2 diabetes susceptibility loci in GWA and RS samples
| Obese type 2 diabetes vs. control subjects
|
Nonobese type 2 diabetes vs. control subjects
|
Pdiff | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Obese type 2 diabetes | Obese type 2 diabetes | RSA + RSB | WTCCC + RS | Passoc | Nonobese type 2 diabetes | Nonobese type 2 diabetes | RSA + RSB | WTCCC + RS | Passoc | ||
| RSA (n = 1,718 /3,596) | RSB (n = 362 /1,750) | RSA (n = 1,407 /3,596) | RSB (n = 270 /1,750) | ||||||||
| rs10811661 (CDKN2B) | 1.17 (1.04–1.31) | 0.98 (0.79–1.22) | 1.12 (1.01–1.24) | 1.13 (1.05–1.24) | 0.002 | 1.25 (1.10–1.42) | 1.28 (0.97–1.68) | 1.25 (1.12–1.41) | 1.26 (1.15–1.38) | 7.0 × 10−7 | 0.09 |
| rs10946398 (CDKAL) | 1.12 (1.03, 1.23) | 1.18 (1.00, 1.40) | 1.13 (1.05–1.23) | 1.14 (1.07–1.21) | 0.00004 | 1.11 (1.01–1.22) | 1.29 (1.06–1.56) | 1.14 (1.05–1.24) | 1.18 (1.11–1.26) | 7.2 × 10−7 | 0.4 |
| rs5015480* (HHEX) | 1.01 (0.93–1.10) | 1.15 (0.97–1.35) | 1.04 (0.96–1.12) | 1.10 (1.03–1.17) | 0.003 | 1.10 (1.01–1.21) | 1.21 (1.00–1.46) | 1.13 (1.03–1.22) | 1.16 (1.08–1.24) | 0.00002 | 0.2 |
| rs13266634† (SLC30A8) | 1.08 (0.99–1.18) | 1.15 (1.00–1.39) | 1.10 (1.01–1.19) | 1.08 (1.01–1.15) | 0.03 | 1.16 (1.06–1.28) | 1.19 (0.96–1.47) | 1.17 (1.07–1.28) | 1.18 (1.10–1.27) | 7.1 × 10−6 | 0.04 |
| rs4402960 (IGF2BP2) | 1.10 (1.00–1.20) | 0.98 (0.82–1.17) | 1.07 (0.99–1.16) | 1.12 (1.05–1.19) | 0.0008 | 1.10 (1.00–1.21) | 1.12 (0.92–1.36) | 1.11 (1.01–1.20) | 1.10 (1.03–1.18) | 0.005 | 0.7 |
| rs564398 (CDKN2B) | 1.17 (1.07–1.28) | 1.03 (0.87–1.22) | 1.14 (1.05–1.22) | 1.15 (1.08–1.22) | 0.00001 | 1.10 (1.00–1.21) | 1.07 (0.89–1.29) | 1.09 (1.01–1.19) | 1.12 (1.05–1.20) | 0.0006 | 0.5 |
| rs2934381 (NOTCH2) | 1.08 (0.94–1.23) | 0.99 (0.76–1.28) | 1.06 (0.944–1.19) | 1.08 (0.98–1.18) | 0.1 | 1.14 (1.00–1.31) | 1.05 (0.78–1.40) | 1.12 (0.99–1.27) | 1.12 (1.02–1.23) | 0.02 | 0.5 |
| rs7578597‡ (THADA) | 1.07 (0.93–1.24) | 1.23 (0.93–1.62) | 1.11 (0.97–1.26) | 1.14 (1.27–1.02) | 0.02 | 1.12 (0.96–1.31) | 1.13 (0.83–1.54) | 1.12 (1.05–1.20) | 1.13 (1.06–1.20) | 0.0002 | 0.5 |
| rs4607103 (ADAMTS9) | 1.04 (0.94–1.15) | 1.13 (0.93–1.37) | 1.06 (0.97–1.16) | 1.10 (1.02–1.18) | 0.02 | 1.06 (0.96–1.18) | 1.05 (0.85–1.31) | 1.01 (0.96–1.17) | 1.09 (1.01–1.17) | 0.04 | 0.9 |
| rs864745 (JAZF1) | 1.04 (0.96–1.13) | 1.40 (1.18–1.65) | 1.10 (1.02–1.19) | 1.12 (1.05–1.19) | 0.0003 | 1.02 (0.93–1.12) | 1.03 (0.85–1.24) | 1.02 (0.94–1.11) | 1.08 (1.01–1.15) | 0.02 | 0.6 |
| rs12779790‡ (CDC123/CAMK1D) | 1.11 (0.99–1.23) | 1.29 (1.05–1.58) | 1.14 (1.04–1.25) | 1.15 (1.06–1.24) | 0.0005 | 1.10 (0.99–1.24) | 1.20 (0.95–1.51) | 1.12 (1.01–1.24) | 1.14 (1.05–1.23) | 0.002 | 0.9 |
| rs7961581 (TSPAN/LGR5) | 1.12 (1.02–1.23) | 0.99 (0.83–1.18) | 1.09 (1.00–1.18) | 1.13 (1.06–1.21) | 0.0002 | 1.06 (0.96–1.17) | 1.16 (0.95–1.41) | 1.07 (0.99–1.16) | 1.13 (1.06–1.20) | 0.0003 | 0.9 |
| rs757210 (HNF1B) | 1.03 (0.95–1.13) | 1.02 (0.86–1.21) | 1.03 (0.96–1.11) | 1.04 (0.97–1.11) | 0.3 | 1.05 (0.96–1.15) | 1.13 (0.94–1.37) | 1.07 (0.98–1.16) | 1.07 (1.00–1.15) | 0.06 | 0.5 |
| rs10010131 (WFS1) | 1.04 (0.96–1.12) | 1.05 (0.88–1.20) | 1.04 (0.97–1.11) | 1.05 (0.99–1.11) | 0.1 | 1.12 (1.04–1.20) | 1.14 (0.96–1.29) | 1.12 (1.05–1.19) | 1.13 (1.06–1.18) | 0.0001 | 0.05 |
| rs1801282 (PPARG) | 1.15 (1.03–1.25) | 1.43 (1.04–1.66) | 1.17 (1.06–1.26) | 1.19 (1.10–1.26) | 0.00004 | 1.10 (0.97–1.21) | 1.19 (0.62–1.53) | 1.11 (0.98–1.21) | 1.13 (1.04–1.22) | 0.006 | 0.3 |
| rs5219 (KCNJ11) | 1.21 (1.11–1.32) | 1.02 (0.86–1.22) | 1.25 (1.15–1.36) | 1.19 (1.11–1.27) | 5.2 × 10−7 | 1.20 (1.10–1.32) | 1.11 (0.91–1.36) | 1.23 (1.13–1.35) | 1.25 (1.16–1.34) | 1.3 × 10−9 | 0.2 |
Stratification in the RS samples is based on the case median BMI from the WTCCC (30.2 kg/m2). Numbers in column headers refer to number of case subjects and control subjects overall. RR estimates by strata are generated from multinomial logistic regression. Passoc represents P value for type 2 diabetes association derived from meta-analysis including WTCCC data; PDIFF represents a test for between-strata heterogeneity. *Meta-analysis only based on rs5015480 and the perfect proxy rs1111875 in RSA and RSB. †rs13266634 (SLC30A8) was not well captured by the Affymetrix chip, so WTCCC data are derived from bespoke genotyping. ‡Imputed genotype data. The CDKN2B locus is represented by two SNPs given evidence of two independent signals in this region (1). Detailed WTCCC results are presented in Supplementary Table S2.