TABLE 1

Associations of 18 SNPs with early-phase insulin release (InsAUC0–30/GluAUC0–30), proinsulin conversion (ProinsAUC0–30/InsAUC0–30), insulin sensitivity (Matsuda ISI), and disposition index (disposition index = InsAUC0–30/GluAUC0–30 × Matsuda ISI) in nondiabetic subjects

Gene SNPAlleles MAF (%)InsAUC0–30 / GluAUC0–30
ProinsAUC0–30 / InsAUC0–30
Matsuda ISI
Disposition index
Effect size B (SE)P values*P valuesEffect size B (SE)P values*P valuesEffect size B (SE)P valuesP valuesEffect size B (SE)P valuesP values
PPARG rs1801282C/G 15.50.63 (0.57)0.3160.6640.14 (0.45)0.9910.560−0.11 (0.11)0.3640.054−0.30 (1.99)0.9580.810
KCNJ11 rs5219G/A 47.7−1.14 (0.41)3.8E-040.0250.49 (0.32)0.1150.5310.25 (0.08)0.0050.008−1.32 (1.40)0.3620.231
TCF7L2 rs7903146C/T 17.7−1.78 (0.53)3.9E-059.8E-070.75 (0.42)0.0026.0E-040.12 (0.11)0.2280.920−6.51 (1.87)8.3E-053.4E-06
SLC30A8 rs13266634C/T 39.1−0.83 (0.41)0.0133.2E-040.73 (0.33)1.9E-051.2E-05−0.00 (0.08)0.8710.679−4.19 (1.46)0.0014.2E-04
HHEX rs1111875C/T 46.9−2.73 (0.40)3.2E-121.4E-140.80 (0.32)9.7E-066.5E-060.17 (0.08)0.0100.017−8.89 (1.42)2.5E-091.2E-10
LOC387761 rs7480010A/G 17.5−0.51 (0.54)0.5400.290−0.33 (0.44)0.8290.1940.17 (0.11)0.0870.3453.57 (1.91)0.0940.189
CDKN2B rs10811661A/G 14.5−1.15 (0.58)0.0211.7E-040.31 (0.47)0.2850.211−0.03 (0.12)0.8470.413−6.30 (1.99)4.3E-040.001
IGF2BP2 rs4402960C/A 32.1−1.34 (0.43)0.0040.0040.14 (0.34)0.2630.3680.08 (0.09)0.1820.440−4.22 (1.53)0.0380.014
CDKAL1 rs7754840G/C 37.0−1.68 (0.42)3.4E-052.2E-060.32 (0.34)3.1E-040.0010.12 (0.08)0.1810.176−5.25 (1.48)1.6E-046.4E-05
WFS1 rs10010131G/A 45.0−0.56 (0.41)0.0480.3970.01 (0.33)0.4020.0810.14 (0.08)0.0550.1000.23 (1.44)0.9860.808
JAZF1 rs864745A/G 48.50.15 (0.41)0.5510.554−0.25 (0.32)0.7920.968−0.10 (0.08)0.1980.067−1.31 (1.43)0.3010.241
CDC123 rs12779790A/G 21.5−0.82 (0.49)0.0590.062−0.07 (0.39)0.4860.5980.07 (0.10)0.3690.433−2.36 (1.73)0.1960.043
TSPAN8 rs7961581A/G 19.40.23 (0.51)0.5250.891−0.29 (0.41)0.1200.310−0.15 (0.10)0.3430.008−0.75 (1.80)0.6350.308
THADA rs7578597A/G 5.0−2.09 (0.93)0.2630.232−1.24 (0.73)0.4250.2670.04 (0.18)0.6590.373−3.51 (3.27)0.3550.410
ADAMTS9 rs4607103G/A 26.1−0.66 (0.47)0.3350.221−0.04 (0.37)0.0870.069−0.04 (0.09)0.8090.587−2.13 (1.65)0.3080.332
NOTCH2 rs10923931C/A 13.8−0.56 (0.59)0.2280.668−0.95 (0.47)0.3600.0800.16 (0.12)0.0540.0601.21 (2.09)0.2440.300
KCNQ1 rs2283228A/C 6.2−1.03 (0.84)0.1610.0930.31 (0.66)0.1760.3530.10 (0.17)0.7010.284−3.29 (2.96)0.1620.221
MTNR1B rs10830963C/G 36.0−2.02 (0.42)1.4E-071.0E-13−0.21 (0.33)0.3010.1890.03 (0.08)0.5770.436−9.65 (1.47)6.7E-113.8E-13
  • Effect size shown is B-coefficient (SE) per copy of the type 2 diabetes risk allele, and was calculated using untransformed variables adjusted for age by linear regression. P values were calculated using log-transformed variables (because of their skewed distribution) by linear regression. P values are adjusted for age;

  • P values are adjusted for age, BMI, and Matsuda ISI;

  • P values are adjusted for age and BMI. In the entire cohort, means ± SE of examined parameters and the number of subjects with available data were as follows: InsAUC0–30/GluAUC0–30 30.4 ± 0.29 pmol/mmol (n = 5,298), ProinsAUC0–30/InsAUC0–30 12.5 ± 0.23 (n = 2,697), Matsuda ISI 7.03 ± 0.06 (mg/dl, mU/l; n = 5,295), and disposition index 163.7 ± 1.02 (n = 5,295). P values significant after correction for multiple testing (P < 6.9 × 10−4) are in bold. Risk alleles are underlined. Results for the additive model are presented.