Supplementary Table 1: a Priori Power Calculations

Supplementary Table 1: A priori power calculations

Phenotype / Study / RAF of Controls / Effect size (OR/β) / Stage 1 / Stage 2 / Combined study population
α=0.05 / α=0.01 / α=0.05 / α=0.01 / α=0.05 / α=0.01
Type 2 diabetes / Europeansa / 0.38 / 1.17 / 70 / 47 / 86 / 69 / 98 / 92
Asian Indian Sikhsb / 0.31 / 1.46 / 99 / 99 / 99 / 99 / 99 / 99
Indo-European Indiansc / 0.30 / 1.26 / 94 / 82 / 99 / 96 / 99 / 99
Dravidian Indiansd / 0.11 / 1.38 / 92 / 80 / -- / -- / -- / --
BMI / Europeanse,f,g / 0.39 / 0.10 / 99 / 99 / 99 / 99 / 99 / 99
Obesity / Europeans (OW+OB vs. NW)e,g / 0.39 / 1.18 / 44 / 22 / 58 / 34 / 81 / 60
Europeans (OB vs. NW)e,g / 0.39 / 1.31 / 77 / 54 / 92 / 79 / 99 / 96
Dravidian Indians (OB vs. NW+ OW) d,h / 0.09 / 2.10 / 99 / 99 / -- / -- / -- / --

Posterior power calculations with respect to different studies have been provided for rs9939609 except for Dravidian Indians where power calculations for rs8050136 have been provided

aScience 316, 1341-1345 (2007)14

bBMC Med Genet9, 59 (2008)11

cDiabetologia52, 247-52 (2009)12

d Diabetes Technol Ther.13,33-42 (2011)13

eScience316, 889-94 (2007)1

fGeometricmean and standard deviation of BMI from UKT2D Genetics Consortium Collection Controls were used for power calculation

gPower calculated for analysis only in control subjects

hPower calculated for analysis in controls and cases combined

OW-Over-weight; OB-Obese; NW-Normal weight

Supplementary Table 2: Power of the present study to detect effect size of previous studies using allele frequency and sample size of the present study

Phenotype / Study / Effect size (OR/β) / Power Stage 1 (α=0.05/ α=0.01) / Stage 2 (α=0.05/ α=0.01) / Combined study population (α=0.05/ α=0.01)
rs1421085 / rs8050136 / rs9939609 / rs9930506 / rs1861867 / rs9926180 / rs2540769 / rs9939609 / rs9926180 / rs9939609 / rs9926180
Type 2 diabetes / Europeans / 1.17 / 69/46 / 68/45 / 68/45 / 72/48 / 66/42 / 60/36 / 66/42 / 85/66 / 80/58 / 97/90 / 95/84
Asian Indian Sikhs / 1.46 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99
Indo-European Indians / 1.26 / 95/86 / 95/85 / 95/85 / 96/88 / 94/82 / 91/76 / 94/83 / 99/99 / 99/99 / 99/99 / 99/99
Dravidian Indians / 1.38 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/98 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99
BMI / Europeansa,b / 0.10 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99
Obesity / Europeans (OW+OB vs. NW)b / 1.18 / 42/21 / 41/20 / 41/20 / 45/23 / 40/20 / 36/17 / 41/20 / 57/33 / 50/27 / 78/57 / 73/50
Europeans (OB vs. NW)b / 1.31 / 75/53 / 74/51 / 74/51 / 78/56 / 73/50 / 68/44 / 74/51 / 90/75 / 87/70 / 99/95 / 98/92
Dravidian Indians (OB vs. NW+ OW)c / 2.10 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / 99/99 / -- / -- / -- / --

aGeometricmean and standard deviation of BMI from UKT2D Genetics Consortium Collection Controls were used for power calculation

bPower calculated for analysis only in control subjects

cPower calculated for analysis in controls and cases combined

OW-Over-weight; OB-Obese; NW-Normal weight

Supplementary Table 3: Allele frequency differences of cases and controlsof the two stages

Subjects / SNP / Minor allele frequency / Chi-square value / P-value
Stage 1 / Stage 2
Controls / rs9939609 / 0.34 / 0.34 / 0.00 / 1
rs9926180 / 0.24 / 0.26 / 3.44 / 0.06
Cases / rs9939609 / 0.35 / 0.35 / 0.01 / 0.92
rs9926180 / 0.27 / 0.25 / 3.58 / 0.06

Supplementary Table 4: Distribution of control subjects based on BMI

Category / Stage 1 / Stage 2 / Combined study
N (%) / Median (IQR) / N (%) / Median (IQR) / N (%) / Median (IQR)
BMI <23.0 / 436(44) / 19.98 (18.19-21.51) / 498(29) / 20.96 (19.26-22.15) / 934(34) / 20.45 (18.58-21.88)
BMI ≥23.0 / 562(56) / 26.43 (24.65-29.05) / 1220(71) / 27.07 (25.01-29.60) / 1782(66) / 26.86 (24.88-29.35)
23.0≤ BMI <25.0 / 174(17) / 24.10 (23.51-24.51) / 300(17) / 24.02 (23.56-24.49) / 474(18) / 24.03 (23.53-24.51)
25.0≤ BMI <27.5 / 141(14) / 25.78 (25.40-26.38) / 294(17) / 25.91 (25.35-26.37) / 435(16) / 25.88 (25.39-26.37)
27.5≤ BMI <30.0 / 136(14) / 28.34 (27.73-28.92) / 356(21) / 28.23 (27.59-28.99) / 492(18) / 28.27 (27.60-28.97)
BMI >30.0 / 111(11) / 32.05 (30.82-34.47) / 270(16) / 32.12 (30.88-34.13) / 381(14) / 32.08 (30.86-34.18)

N - number of individuals; IQR – inter quartile range

Supplementary Table 5: Association of variants with obesity defined on the basis of waist circumference and waist to hip ratio

Study / SNP / WC defined obesity / WHR defined obesity
Allele (Minor/Major) / N (OB/ NW) / MAF (OB/ NW) / OR (95% CI) / P-value / Allele (Minor/Major) / N (OB/ NW) / MAF (OB/ NW) / OR (95% CI) / P-value
Stage 1a / rs1421085 / C/T / 491/ 500 / 0.37/ 0.34 / 1.14 (0.94-1.37) / 0.18 / C/T / 654/ 337 / 0.36/ 0.35 / 1.05 (0.86-1.28) / 0.62
rs8050136 / A/C / 491/ 500 / 0.36/ 0.32 / 1.16 (0.96-1.40) / 0.13 / A/C / 654/ 337 / 0.35/ 0.33 / 1.07 (0.87-1.31) / 0.50
rs9939609 / A/T / 492/ 500 / 0.36/ 0.32 / 1.15 (0.95-1.39) / 0.15 / A/T / 655/ 337 / 0.35/ 0.33 / 1.07 (0.88-1.32) / 0.50
rs9930506 / G/A / 471/ 471 / 0.43/ 0.43 / 0.99 (0.83-1.19) / 0.93 / G/A / 622/ 320 / 0.43/ 0.44 / 0.96 (0.79-1.16) / 0.65
rs1861867 / T/C / 492/ 500 / 0.29/ 0.31 / 0.90 (0.74-1.09) / 0.28 / T/C / 655/ 337 / 0.29/ 0.30 / 0.97 (0.79-1.20) / 0.78
rs9926180 / A/T / 488/ 493 / 0.23/ 0.24 / 0.96 (0.78-1.19) / 0.72 / A/T / 645/ 336 / 0.23/ 0.26 / 0.85 (0.68-1.07) / 0.16
rs2540769 / G/T / 492/ 500 / 0.31/ 0.31 / 1.01 (0.83-1.23) / 0.92 / G/T / 655/ 337 / 0.31/ 0.31 / 1.06 (0.86-1.31) / 0.58
Stage 2a / rs1421085 / C/T / 370/209 / 0.38/0.31 / 1.43 (1.11-1.85) / 0.006 / C/T / 363/192 / 0.37/0.32 / 1.38 (1.04-1.83) / 0.02
rs8050136 / A/C / 393/224 / 0.34/0.30 / 1.17 (0.91-1.51) / 0.22 / A/C / 395/197 / 0.34/0.30 / 1.30 (0.98-1.73) / 0.07
rs9939609 / A/T / 882/687 / 0.35/0.33 / 1.10 (0.94-1.27) / 0.23 / A/T / 1092/452 / 0.34/0.33 / 1.10 (0.93-1.30) / 0.28
rs9930506 / G/A / 391/222 / 0.46/0.39 / 1.37 (1.07-1.77) / 0.01 / G/A / 390/198 / 0.45/0.38 / 1.39 (1.05-1.84) / 0.02
rs9926180 / A/T / 784/648 / 0.25/0.26 / 0.93 (0.78-1.09) / 0.36 / A/T / 994/413 / 0.25/0.26 / 0.95 (0.79-1.15) / 0.6
Combined Study Populationb / rs1421085 / C/T / 861/709 / 0.38/0.33 / 1.23 (1.06-1.43) / 0.006 / C/T / 1017/529 / 0.37/0.34 / 1.15 (0.97-1.35) / 0.10
rs8050136 / A/C / 884/724 / 0.35/0.32 / 1.17 (1.00-1.36) / 0.05 / A/C / 1049/534 / 0.34/0.32 / 1.14 (0.97-1.35) / 0.12
rs9939609 / A/T / 1374/1187 / 0.35/0.33 / 1.12 (1.00-1.26) / 0.06 / A/T / 1747/789 / 0.34/0.33 / 1.09 (0.95-1.24) / 0.21
rs9930506 / G/A / 862/693 / 0.44/0.42 / 1.11 (0.96-1.29) / 0.15 / G/A / 1012/518 / 0.44/0.42 / 1.08 (0.92-1.27) / 0.34
rs9926180 / A/T / 1272/1141 / 0.24/0.25 / 0.94 (0.83-1.08) / 0.38 / A/T / 1639/749 / 0.24/0.26 / 0.91 (0.79-1.05) / 0.20

WC- waist circumference; WHR- waist to hip ratio; N- number of individuals; MAF- minor allele frequency; OR- odds ratio; CI- confidence interval; OB- obese; NW- normal weight

aAnalysis adjusted for sex and age

bAnalysis adjusted for sex, age and study

Supplementary Table 6: Association of variants with quantitative traits in stage 1

Trait / SNP / Minor allele / N / Mean ± SD / β (95%CI) / P-value
aa / ab / bb
BMI (Kg/m2)a / rs1421085 / C / 997 / 24.35±4.73 / 24.26±4.98 / 23.67±4.88 / 0.407 (-0.026-0.841) / 0.07
rs8050136 / A / 997 / 24.28±4.81 / 24.33±4.99 / 23.67±4.85 / 0.402 (-0.038-0.842) / 0.07
rs9939609 / A / 998 / 24.26±4.82 / 24.34±4.98 / 23.67±4.86 / 0.398 (-0.044-0.839) / 0.08
rs9930506 / G / 948 / 23.74±5.04 / 24.23±4.98 / 23.9±4.81 / -0.042 (-0.466-0.382) / 0.85
rs1861867 / T / 998 / 23.82±4.83 / 23.81±4.91 / 24.26±4.93 / -0.321 (-0.783-0.141) / 0.17
rs9926180 / A / 987 / 24.19±5.13 / 23.8±4.87 / 24.16±4.95 / -0.19 (-0.695-0.315) / 0.46
rs2540769 / G / 998 / 24.12±4.88 / 23.91±4.8 / 24.13±5.03 / -0.001 (-0.456-0.454) / 1.00
Waist (cm)a / rs1421085 / C / 991 / 88.1±11.04 / 87.48±11.32 / 86.07±11.83 / 1.108 (0.08-2.136) / 0.04
rs8050136 / A / 991 / 87.92±11.46 / 87.69±11.37 / 86±11.63 / 1.183 (0.14-2.226) / 0.03
rs9939609 / A / 992 / 87.85±11.48 / 87.7±11.34 / 86±11.64 / 1.168 (0.123-2.212) / 0.03
rs9930506 / G / 942 / 87.18±12.04 / 87.37±11.38 / 86.26±11.52 / 0.535 (-0.469-1.54) / 0.30
rs1861867 / T / 992 / 85.65±10.99 / 86.43±11.74 / 87.65±11.39 / -1.051 (-2.145-0.044) / 0.06
rs9926180 / A / 981 / 87.51±10.44 / 86.84±11.72 / 86.95±11.55 / 0.089 (-1.108-1.285) / 0.88
rs2540769 / G / 992 / 88.13±11.25 / 86.95±11.62 / 86.74±11.48 / 0.369 (-0.712-1.449) / 0.50
WHRa / rs1421085 / C / 991 / 0.93±0.08 / 0.93±0.09 / 0.92±0.08 / 0.006 (0-0.012) / 0.07
rs8050136 / A / 991 / 0.93±0.08 / 0.93±0.08 / 0.92±0.08 / 0.006 (0-0.013) / 0.06
rs9939609 / A / 992 / 0.93±0.08 / 0.93±0.08 / 0.92±0.08 / 0.006 (0-0.013) / 0.06
rs9930506 / G / 942 / 0.92±0.08 / 0.92±0.08 / 0.92±0.09 / 0.002 (-0.005-0.008) / 0.62
rs1861867 / T / 992 / 0.91±0.08 / 0.92±0.08 / 0.93±0.08 / -0.005 (-0.012-0.002) / 0.15
rs9926180 / A / 981 / 0.93±0.08 / 0.92±0.08 / 0.92±0.08 / -0.002 (-0.009-0.006) / 0.64
rs2540769 / G / 992 / 0.93±0.08 / 0.93±0.09 / 0.92±0.08 / 0.004 (-0.003-0.011) / 0.24
FPG (mmol/l)b / rs1421085 / C / 977 / 4.88±0.57 / 4.84±0.62 / 4.84±0.66 / 0.004 (-0.053-0.061) / 0.90
rs8050136 / A / 977 / 4.87±0.57 / 4.85±0.62 / 4.84±0.66 / 0.003 (-0.054-0.061) / 0.91
rs9939609 / A / 978 / 4.87±0.57 / 4.85±0.62 / 4.84±0.66 / 0.003 (-0.055-0.061) / 0.92
rs9930506 / G / 928 / 4.87±0.6 / 4.87±0.63 / 4.82±0.67 / 0.029 (-0.027-0.085) / 0.31
rs1861867 / T / 978 / 4.81±0.72 / 4.84±0.62 / 4.86±0.63 / -0.022 (-0.082-0.038) / 0.48
rs9926180 / A / 967 / 4.9±0.61 / 4.83±0.61 / 4.86±0.65 / 0.004 (-0.062-0.069) / 0.92
rs2540769 / G / 978 / 4.73±0.6 / 4.86±0.62 / 4.87±0.65 / -0.051 (-0.11-0.009) / 0.10
2 hr. PPG (mmol/L)b / rs1421085 / C / 192 / 5.75±1.06 / 5.57±1.05 / 5.46±1.16 / 0.152 (-0.074-0.377) / 0.19
rs8050136 / A / 192 / 5.81±1.1 / 5.58±1.04 / 5.44±1.14 / 0.189 (-0.039-0.417) / 0.11
rs9939609 / A / 192 / 5.8±1.13 / 5.57±1.03 / 5.45±1.15 / 0.178 (-0.053-0.408) / 0.13
rs9930506 / G / 182 / 5.75±1.07 / 5.6±1.05 / 5.42±1.13 / 0.177 (-0.045-0.399) / 0.12
rs1861867 / T / 192 / 5.8±0.84 / 5.42±1.13 / 5.61±1.09 / -0.015 (-0.257-0.227) / 0.90
rs9926180 / A / 190 / 5.6±0.91 / 5.52±1.07 / 5.58±1.12 / -0.004 (-0.275-0.268) / 0.98
rs2540769 / G / 192 / 5.87±1.05 / 5.43±1.12 / 5.59±1.06 / 0.017 (-0.222-0.255) / 0.89
HbA1C (%)b / rs1421085 / C / 999 / 5.21±0.48 / 5.24±0.49 / 5.18±0.47 / 0.017 (-0.025-0.058) / 0.43
rs8050136 / A / 999 / 5.23±0.47 / 5.23±0.49 / 5.18±0.47 / 0.018 (-0.024-0.06) / 0.39
rs9939609 / A / 1000 / 5.23±0.47 / 5.23±0.49 / 5.18±0.47 / 0.018 (-0.024-0.06) / 0.40
rs9930506 / G / 950 / 5.24±0.48 / 5.23±0.5 / 5.18±0.47 / 0.028 (-0.013-0.068) / 0.18
rs1861867 / T / 1000 / 5.12±0.5 / 5.2±0.48 / 5.23±0.48 / -0.035 (-0.079-0.009) / 0.12
rs9926180 / A / 989 / 5.27±0.49 / 5.21±0.51 / 5.2±0.46 / 0.035 (-0.013-0.083) / 0.15
rs2540769 / G / 1000 / 5.2±0.5 / 5.2±0.47 / 5.22±0.48 / -0.019 (-0.062-0.024) / 0.39
FPI (pmol/L)b / rs1421085 / C / 888 / 42.56±52.65 / 47.68±48.4 / 44.86±50.4 / -1.597 (-6.075-2.88) / 0.48
rs8050136 / A / 888 / 41.34±53.57 / 48.16±48.04 / 44.75±50.47 / -1.793 (-6.339-2.752) / 0.44
rs9939609 / A / 889 / 41.42±53.82 / 48.05±47.92 / 44.85±50.49 / -1.845 (-6.398-2.707) / 0.43
rs9930506 / G / 845 / 44.53±55.4 / 50.03±48.38 / 43.47±48.5 / 0.853 (-3.477-5.183) / 0.70
rs1861867 / T / 889 / 44.5±48.67 / 43.91±48.43 / 47.67±51.1 / -1.767 (-6.481-2.947) / 0.46
rs9926180 / A / 878 / 42.35±54.13 / 47.05±49.58 / 45.71±49.95 / 0.563 (-4.581-5.706) / 0.83
rs2540769 / G / 889 / 40.81±42.56 / 45.5±49.86 / 47.18±51.1 / -1.714 (-6.384-2.957) / 0.47
HOMA IRb / rs1421085 / C / 872 / 1.6±1.99 / 1.75±1.85 / 1.62±1.89 / -0.032 (-0.203-0.14) / 0.72
rs8050136 / A / 872 / 1.55±2.02 / 1.77±1.83 / 1.61±1.89 / -0.038 (-0.212-0.136) / 0.67
rs9939609 / A / 873 / 1.55±2.03 / 1.77±1.83 / 1.62±1.9 / -0.04 (-0.215-0.134) / 0.65
rs9930506 / G / 829 / 1.65±2.07 / 1.84±1.84 / 1.55±1.83 / 0.062 (-0.103-0.228) / 0.46
rs1861867 / T / 873 / 1.6±1.86 / 1.61±1.83 / 1.75±1.93 / -0.074 (-0.253-0.104) / 0.42
rs9926180 / A / 862 / 1.59±2.08 / 1.72±1.87 / 1.66±1.89 / 0.032 (-0.164-0.227) / 0.75
rs2540769 / G / 873 / 1.45±1.59 / 1.67±1.88 / 1.73±1.93 / -0.078 (-0.255-0.1) / 0.39
C-peptide (nmol/L)b / rs1421085 / C / 891 / 0.57±0.37 / 0.62±0.33 / 0.59±0.35 / -0.016 (-0.047-0.015) / 0.32
rs8050136 / A / 891 / 0.54±0.37 / 0.63±0.33 / 0.59±0.34 / -0.019 (-0.05-0.012) / 0.23
rs9939609 / A / 892 / 0.54±0.37 / 0.63±0.33 / 0.59±0.34 / -0.02 (-0.051-0.011) / 0.21
rs9930506 / G / 846 / 0.57±0.37 / 0.61±0.32 / 0.6±0.35 / -0.017 (-0.047-0.013) / 0.27
rs1861867 / T / 892 / 0.63±0.38 / 0.59±0.33 / 0.61±0.34 / 0.004 (-0.029-0.036) / 0.83
rs9926180 / A / 881 / 0.57±0.37 / 0.61±0.32 / 0.6±0.35 / 0.006 (-0.03-0.041) / 0.75
rs2540769 / G / 892 / 0.57±0.29 / 0.62±0.34 / 0.59±0.35 / 0.002 (-0.03-0.034) / 0.90
hsCRP (mg/L)b / rs1421085 / C / 897 / 2.13±1.86 / 1.93±2.06 / 1.93±1.97 / 0.024 (-0.16-0.207) / 0.80
rs8050136 / A / 897 / 2.19±1.82 / 1.94±2.05 / 1.89±1.98 / 0.068 (-0.119-0.254) / 0.48
rs9939609 / A / 898 / 2.22±1.81 / 1.94±2.05 / 1.89±1.99 / 0.073 (-0.115-0.26) / 0.45
rs9930506 / G / 851 / 2.11±1.96 / 1.98±2.02 / 1.96±2.02 / 0.067 (-0.113-0.247) / 0.47
rs1861867 / T / 898 / 1.89±2.32 / 1.96±1.83 / 1.96±2.06 / 0.011 (-0.184-0.206) / 0.91
rs9926180 / A / 887 / 2.14±1.9 / 1.83±2.08 / 2.01±1.95 / -0.034 (-0.245-0.178) / 0.75
rs2540769 / G / 898 / 1.73±1.98 / 2.08±2.05 / 1.89±1.95 / 0.027 (-0.166-0.219) / 0.79
TC (mmol/L)b / rs1421085 / C / 988 / 4.4±1.13 / 4.54±1.01 / 4.43±1.07 / 0.004 (-0.09-0.098) / 0.93
rs8050136 / A / 988 / 4.36±1.09 / 4.55±1.02 / 4.43±1.07 / -0.003 (-0.098-0.093) / 0.95
rs9939609 / A / 989 / 4.36±1.09 / 4.54±1.02 / 4.43±1.07 / -0.004 (-0.1-0.091) / 0.93
rs9930506 / G / 939 / 4.33±1.04 / 4.55±1.06 / 4.44±1.03 / -0.041 (-0.132-0.049) / 0.37
rs1861867 / T / 989 / 4.36±1.16 / 4.51±1.05 / 4.46±1.03 / -6.348 (3-0.09969-0.1) / 1.00
rs9926180 / A / 978 / 4.35±0.83 / 4.45±1.11 / 4.5±1.03 / -0.047 (-0.156-0.061) / 0.39
rs2540769 / G / 989 / 4.34±1.06 / 4.47±1.04 / 4.5±1.06 / -0.06 (-0.158-0.039) / 0.23
HDL-C (mmol/L)b / rs1421085 / C / 893 / 1.1±0.36 / 1.12±0.36 / 1.12±0.36 / -0.008 (-0.041-0.026) / 0.66
rs8050136 / A / 893 / 1.09±0.36 / 1.12±0.37 / 1.12±0.36 / -0.011 (-0.045-0.022) / 0.52
rs9939609 / A / 894 / 1.09±0.36 / 1.13±0.36 / 1.12±0.36 / -0.012 (-0.046-0.022) / 0.48
rs9930506 / G / 844 / 1.1±0.39 / 1.15±0.35 / 1.09±0.37 / 0.009 (-0.024-0.041) / 0.60
rs1861867 / T / 894 / 1.07±0.37 / 1.13±0.37 / 1.11±0.36 / -0.001 (-0.036-0.034) / 0.94
rs9926180 / A / 883 / 0.99±0.37 / 1.1±0.35 / 1.14±0.37 / -0.06 (-0.098--0.022) / 0.002
rs2540769 / G / 894 / 1.1±0.36 / 1.11±0.37 / 1.12±0.36 / -0.008 (-0.043-0.027) / 0.65
LDL-C (mmol/L)b / rs1421085 / C / 988 / 2.87±0.88 / 2.95±0.83 / 2.81±0.89 / 0.049 (-0.029-0.127) / 0.22
rs8050136 / A / 988 / 2.85±0.85 / 2.96±0.84 / 2.81±0.9 / 0.049 (-0.03-0.128) / 0.22
rs9939609 / A / 989 / 2.85±0.85 / 2.96±0.84 / 2.81±0.9 / 0.048 (-0.031-0.127) / 0.23
rs9930506 / G / 939 / 2.77±0.87 / 2.96±0.85 / 2.84±0.87 / -0.019 (-0.094-0.057) / 0.63
rs1861867 / T / 989 / 2.76±1 / 2.88±0.84 / 2.9±0.86 / -0.045 (-0.128-0.038) / 0.29
rs9926180 / A / 978 / 2.82±0.7 / 2.89±0.93 / 2.88±0.84 / -0.008 (-0.098-0.082) / 0.86
rs2540769 / G / 989 / 2.81±0.88 / 2.9±0.87 / 2.88±0.86 / -0.012 (-0.093-0.069) / 0.77
TG (mmol/L)b / rs1421085 / C / 988 / 1.55±0.88 / 1.57±0.85 / 1.51±0.88 / 0.049 (-0.029-0.127) / 0.22
rs8050136 / A / 988 / 1.51±0.88 / 1.59±0.84 / 1.51±0.89 / 0.049 (-0.03-0.128) / 0.22
rs9939609 / A / 989 / 1.52±0.87 / 1.58±0.84 / 1.51±0.89 / 0.048 (-0.031-0.127) / 0.23
rs9930506 / G / 939 / 1.53±0.87 / 1.57±0.81 / 1.5±0.94 / -0.019 (-0.094-0.057) / 0.63
rs1861867 / T / 989 / 1.55±0.98 / 1.53±0.87 / 1.55±0.85 / -0.045 (-0.128-0.038) / 0.29
rs9926180 / A / 978 / 1.62±0.93 / 1.53±0.85 / 1.54±0.87 / -0.008 (-0.098-0.082) / 0.86
rs2540769 / G / 989 / 1.34±0.84 / 1.54±0.9 / 1.59±0.84 / -0.012 (-0.093-0.069) / 0.77
Blood Urea (mmol/L)b / rs1421085 / C / 989 / 9.02±2.86 / 8.89±3.15 / 8.74±2.97 / 0.017 (-0.059-0.093) / 0.66
rs8050136 / A / 989 / 8.94±2.81 / 8.91±3.17 / 8.76±2.96 / 0.013 (-0.064-0.09) / 0.74
rs9939609 / A / 990 / 8.91±2.81 / 8.92±3.16 / 8.76±2.97 / 0.013 (-0.064-0.091) / 0.73
rs9930506 / G / 940 / 8.99±2.93 / 8.82±3.16 / 8.86±2.92 / 0.023 (-0.051-0.097) / 0.54
rs1861867 / T / 990 / 8.69±2.76 / 8.67±3.09 / 9.02±3.04 / 0.002 (-0.078-0.083) / 0.95
rs9926180 / A / 979 / 8.58±2.73 / 8.72±3.08 / 8.94±3.01 / 0.018 (-0.069-0.105) / 0.69
rs2540769 / G / 990 / 8.95±2.83 / 8.93±3.08 / 8.75±3.04 / -0.091 (-0.17--0.012) / 0.02
Uric acid (umol/L)b / rs1421085 / C / 933 / 312.5±213.7 / 299.8±232.2 / 300.5±224.5 / 0.142 (-0.132-0.416) / 0.31
rs8050136 / A / 933 / 304.5±209.5 / 300.7±235.8 / 302.3±221.7 / 0.092 (-0.187-0.372) / 0.52
rs9939609 / A / 933 / 303.7±210.3 / 301.1±235.3 / 302.1±221.9 / 0.088 (-0.192-0.368) / 0.54
rs9930506 / G / 883 / 301.1±197 / 276.9±229.2 / 317±232.8 / 0.032 (-0.233-0.297) / 0.81
rs1861867 / T / 933 / 290.9±247.8 / 289.3±229.3 / 314.3±219.5 / -0.23 (-0.518-0.059) / 0.12
rs9926180 / A / 922 / 270±227.4 / 301.3±245.1 / 300.9±213.1 / -0.142 (-0.459-0.174) / 0.38
rs2540769 / G / 933 / 298.6±224.9 / 309.8±228.3 / 295.4±225.1 / 0.079 (-0.208-0.367) / 0.59
Creatinine (umol/L)b / rs1421085 / C / 900 / 88.3±160.2 / 71.77±160.8 / 78.88±163.7 / 2.166 (-17.26-21.59) / 0.83
rs8050136 / A / 900 / 86.01±161.8 / 73.73±162.7 / 77.73±161.3 / -0.029 (-19.78-19.72) / 1.00
rs9939609 / A / 900 / 85.21±162.3 / 73.88±162.4 / 77.84±161.5 / 0.000 (-19.800-19.800) / 1.00
rs9930506 / G / 850 / 89.07±165.1 / 68.93±162.6 / 72.5±159.7 / -8.231 (-27.03-10.57) / 0.39
rs1861867 / T / 900 / 78.24±180.3 / 67.6±160.3 / 84.65±159.5 / -16.25 (-36.86-4.358) / 0.12
rs9926180 / A / 889 / 44.92±144.3 / 88.19±165.1 / 72.2±161.2 / -6.309 (-28.79-16.17) / 0.58
rs2540769 / G / 900 / 84.13±152 / 85.37±162.2 / 67.95±163.4 / 4.505 (-15.96-24.97) / 0.67
Systolic BP (mmHg)b / rs1421085 / C / 887 / 122.8±20.32 / 126.7±18.21 / 126.4±19.15 / 2.67 (-10.94-16.28) / 0.70
rs8050136 / A / 887 / 122.6±21.03 / 126.6±18.26 / 126.3±18.93 / 3.529 (-10.29-17.35) / 0.62
rs9939609 / A / 887 / 122.6±21.13 / 126.6±18.24 / 126.4±18.93 / 3.296 (-10.55-17.15) / 0.64
rs9930506 / G / 837 / 124.3±20.72 / 127±18.7 / 126.4±18.59 / 8.896 (-4.205-22) / 0.18
rs1861867 / T / 887 / 126.8±17.8 / 125.1±18.46 / 126.6±19.53 / -9.544 (-23.93-4.847) / 0.19
rs9926180 / A / 876 / 125.8±19.72 / 124.8±17.86 / 126.7±19.32 / 3.84 (-11.77-19.45) / 0.63
rs2540769 / G / 887 / 128.1±20.85 / 125.7±18.69 / 125.8±18.73 / 6.368 (-7.882-20.62) / 0.38
Diasystolic BP (mmHg)b / rs1421085 / C / 911 / 78.5±11.74 / 80.18±10.87 / 80.38±10.95 / -1.733 (-3.392--0.075) / 0.04
rs8050136 / A / 911 / 78.22±11.5 / 80.22±11.01 / 80.35±10.91 / -1.918 (-3.607--0.23) / 0.03
rs9939609 / A / 911 / 78.24±11.55 / 80.18±11 / 80.37±10.91 / -1.941 (-3.633--0.248) / 0.02
rs9930506 / G / 861 / 78.88±11.47 / 80.19±10.59 / 80.56±11.57 / -1.136 (-2.758-0.487) / 0.17
rs1861867 / T / 911 / 80.3±10.5 / 80.03±10.69 / 79.99±11.43 / -0.293 (-2.048-1.462) / 0.74
rs9926180 / A / 900 / 79.11±10.98 / 79.4±10.92 / 80.35±11.03 / -0.676 (-2.596-1.244) / 0.49
rs2540769 / G / 911 / 80.74±11.55 / 79.97±11.36 / 79.94±10.64 / 0.827 (-0.909-2.563) / 0.35

Data are presented as mean ± standard deviations

aa: minor allele homozygous; ab: heterozygous; bb: major allele homozygous

N- number if Individuals; BMI- Body mass index; WC- Waist circumference; WHR- Waist hip ratio; FPG- Fasting plasma glucose; 2h PPG- 2 hrs post prandial glucose; HbA1c- Glycosylated haemoglobin A1c; FPI- Fasting plasma insulin; HOMA-IR- Homeostasis model assessment for insulin resistance; hsCRP- high sensitivity C-reactive protein; TC- Total cholesterol; HDL-C- High density lipoprotein cholesterol; LDL-C- Low density lipoprotein cholesterol; TG- Triglycerides; BP- blood pressure

aAnalysis adjusted for sex and age

bAnalysis adjusted for sex, age and BMI

Supplementary Table 7: Association of variants with quantitative traits in stage 2

Triat / SNP / A1 / NMISS / Mean ± SD / β (95% CI) / P
aa / ab / bb
BMI (Kg/m2)a / rs1421085 / C / 629 / 26.59±4.43 / 25.66±4.66 / 24.65±4.66 / 0.999(0.479-1.519) / 0.0002
rs8050136 / A / 673 / 26.03±4.62 / 25.83±4.82 / 24.69±4.38 / 0.81(0.292-1.327) / 0.002
rs9939609 / A / 1628 / 25.85±4.89 / 25.75±4.59 / 25.35±4.67 / 0.271(-0.061-0.602) / 0.11
rs9930506 / G / 667 / 25.86±4.5 / 25.52±4.73 / 24.74±4.48 / 0.543(0.028-1.057) / 0.04
rs9926180 / A / 1490 / 25.93±4.15 / 25.24±4.71 / 25.87±4.75 / -0.269(-0.644-0.106) / 0.16
Waist (cm)a / rs1421085 / C / 579 / 94.09±11.06 / 90.58±11.38 / 89.02±10.79 / 2.195(0.88-3.51) / 0.001
rs8050136 / A / 617 / 91.71±11.76 / 91.01±11.86 / 89.41±10.46 / 1.346(0.005-2.688) / 0.05
rs9939609 / A / 1569 / 92.42±11.67 / 90.85±11.37 / 90.36±11.14 / 0.913(0.101-1.724) / 0.03
rs9930506 / G / 613 / 92.03±11.23 / 90.68±11.46 / 89.06±10.75 / 1.588(0.282-2.893) / 0.02
rs9926180 / A / 1432 / 91.79±11.2 / 89.72±11.11 / 91.28±11.41 / -0.629(-1.54-0.281) / 0.18
WHRa / rs1421085 / C / 555 / 0.93±0.08 / 0.92±0.07 / 0.92±0.07 / 0.003(-0.006-0.011) / 0.53
rs8050136 / A / 592 / 0.94±0.07 / 0.92±0.07 / 0.93±0.07 / 0.003(-0.005-0.011) / 0.44
rs9939609 / A / 1544 / 0.92±0.08 / 0.92±0.08 / 0.92±0.08 / 0.003(-0.002-0.008) / 0.22
rs9930506 / G / 588 / 0.92±0.07 / 0.93±0.07 / 0.92±0.07 / 0.004(-0.004-0.012) / 0.37
rs9926180 / A / 1407 / 0.92±0.09 / 0.92±0.08 / 0.92±0.09 / -0.001(-0.007-0.005) / 0.75
FPG (mmol/l)b / rs1421085 / C / 610 / 4.71±0.61 / 4.71±0.53 / 4.72±0.57 / -0.03(-0.091-0.03) / 0.33
rs8050136 / A / 653 / 4.73±0.63 / 4.71±0.53 / 4.72±0.57 / -0.01(-0.07-0.05) / 0.74
rs9939609 / A / 1608 / 4.75±0.63 / 4.77±0.61 / 4.81±0.6 / -0.031(-0.074-0.012) / 0.16
rs9930506 / G / 647 / 4.65±0.6 / 4.74±0.55 / 4.71±0.51 / 0.01(-0.049-0.069) / 0.73
rs9926180 / A / 1470 / 4.74±0.66 / 4.76±0.61 / 4.77±0.61 / -0.001(-0.05-0.048) / 0.98
2 hr. PPG (mmol/L)b / rs1421085 / C / 241 / 5.86±1.07 / 5.91±1.23 / 5.82±1.02 / 0.038(-0.149-0.224) / 0.69
rs8050136 / A / 265 / 6.01±1.14 / 5.88±1.19 / 5.8±1.01 / -0.025(-0.2-0.151) / 0.78
rs9939609 / A / 543 / 5.71±0.93 / 5.74±1.11 / 5.68±1.08 / 0.034(-0.098-0.166) / 0.62
rs9930506 / G / 261 / 6.02±1.02 / 5.83±1.16 / 5.76±1.05 / 0.001(-0.176-0.178) / 0.99
rs9926180 / A / 485 / 5.54±1.17 / 5.75±1.07 / 5.72±1.06 / -0.112(-0.257-0.033) / 0.13
HbA1C (%)b / rs1421085 / C / 458 / 5.81±0.41 / 5.79±0.39 / 5.79±0.37 / -0.002(-0.053-0.049) / 0.94
rs8050136 / A / 493 / 5.78±0.41 / 5.78±0.38 / 5.8±0.38 / -0.022(-0.073-0.029) / 0.40
rs9939609 / A / 1449 / 5.61±0.4 / 5.64±0.38 / 5.65±0.38 / -0.017(-0.046-0.013) / 0.27
rs9930506 / G / 491 / 5.71±0.4 / 5.83±0.37 / 5.76±0.38 / -0.012(-0.062-0.038) / 0.64
rs9926180 / A / 1313 / 5.56±0.39 / 5.61±0.36 / 5.61±0.37 / -0.006(-0.037-0.026) / 0.72
FPI (pmol/L)b / rs1421085 / C / 10 / 54.41±49.91 / 23.99±15.51 / 42.78±21.69 / -7.787(-28.19-12.62) / 0.49
rs8050136 / A / 9 / 82.45±16.24 / 33.46±38.81 / 42.63±24.47 / -0.545(-32.29-31.2) / 0.97
rs9939609 / A / 886 / 50.94±43.54 / 50.04±36.69 / 54.35±37.38 / -2.237(-5.464-0.991) / 0.17
rs9930506 / G / 11 / 42.6±47.1 / 46.14±34.49 / 49.45±20.95 / -10.23(-26.41-5.951) / 0.26
rs9926180 / A / 921 / 57.86±36.8 / 49.99±38.03 / 52.42±38.42 / 2.269(-1.181-5.72) / 0.20
HOMA IRb / rs1421085 / C / 10 / 1.76±1.79 / 0.73±0.8 / 1.54±0.82 / -0.402(-1.209-0.405) / 0.37
rs8050136 / A / 9 / 2.78±0.46 / 1.13±1.61 / 1.59±0.89 / -0.215(-1.522-1.092) / 0.76
rs9939609 / A / 885 / 1.83±1.7 / 1.8±1.48 / 2.02±1.54 / -0.12(-0.251-0.012) / 0.08
rs9930506 / G / 11 / 1.29±1.73 / 1.68±1.4 / 1.82±0.74 / -0.535(-1.158-0.088) / 0.14
rs9926180 / A / 919 / 2.08±1.49 / 1.82±1.54 / 1.92±1.56 / 0.074(-0.067-0.215) / 0.31
C-peptide (nmol/L)b / rs1421085 / C / 0 / -- / -- / -- / -- / --
rs8050136 / A / 0 / -- / -- / -- / -- / --
rs9939609 / A / 875 / 0.6888±0.3532 / 0.7337±0.3117 / 0.7426±0.3379 / -0.02 (-0.05-0.01) / 0.23
rs9930506 / G / 0 / -- / -- / -- / -- / --
rs9926180 / A / 910 / 0.7757±0.3372 / 0.7035±0.322 / 0.7385±0.3332 / 0.01 (-0.02-0.04) / 0.62
hsCRP (mg/L)b / rs1421085 / C / 413 / 2.32±1.85 / 2.61±1.87 / 2.69±2.15 / -0.257(-0.538-0.024) / 0.07
rs8050136 / A / 446 / 2.31±1.78 / 2.64±2 / 2.66±2.13 / -0.208(-0.493-0.077) / 0.15
rs9939609 / A / 1318 / 2.46±2.04 / 2.4±2.09 / 2.41±2.04 / -0.022(-0.182-0.139) / 0.79
rs9930506 / G / 443 / 2.23±1.86 / 2.73±2.07 / 2.61±2.02 / -0.189(-0.469-0.092) / 0.19
rs9926180 / A / 1185 / 2.47±2.08 / 2.33±2.09 / 2.35±2.08 / 0.08(-0.099-0.258) / 0.38
TC (mmol/L)b / rs1421085 / C / 561 / 4.96±1.17 / 4.77±1.06 / 4.76±1.05 / 0.079(-0.052-0.209) / 0.24
rs8050136 / A / 599 / 4.79±1.13 / 4.83±1.07 / 4.73±1.05 / 0.045(-0.085-0.175) / 0.50
rs9939609 / A / 1545 / 4.92±1.02 / 4.9±1.04 / 4.88±1.08 / 0.031(-0.047-0.108) / 0.44
rs9930506 / G / 595 / 4.78±1.12 / 4.84±1.08 / 4.68±1.04 / 0.066(-0.064-0.195) / 0.32
rs9926180 / A / 1406 / 4.96±1.07 / 4.8±1 / 4.97±1.04 / -0.069(-0.154-0.016) / 0.11
HDL-C (mmol/L)b / rs1421085 / C / 561 / 1.12±0.33 / 1.18±0.37 / 1.18±0.34 / -0.014(-0.056-0.028) / 0.51
rs8050136 / A / 599 / 1.14±0.31 / 1.18±0.34 / 1.17±0.36 / -0.004(-0.045-0.037) / 0.83
rs9939609 / A / 1549 / 1.21±0.33 / 1.25±0.33 / 1.25±0.34 / -0.007(-0.031-0.016) / 0.53
rs9930506 / G / 595 / 1.19±0.37 / 1.17±0.34 / 1.16±0.35 / 0.01(-0.03-0.051) / 0.63
rs9926180 / A / 1412 / 1.22±0.34 / 1.27±0.32 / 1.27±0.34 / -0.007(-0.033-0.019) / 0.61
LDL-C (mmol/L)b / rs1421085 / C / 561 / 3.17±0.97 / 2.96±0.85 / 2.93±0.86 / 0.092(-0.014-0.199) / 0.09
rs8050136 / A / 599 / 3.05±0.98 / 3±0.85 / 2.9±0.86 / 0.076(-0.03-0.183) / 0.16
rs9939609 / A / 1555 / 3.09±0.84 / 3.02±0.84 / 3.01±0.88 / 0.035(-0.028-0.098) / 0.28
rs9930506 / G / 595 / 2.98±0.95 / 3.03±0.85 / 2.85±0.87 / 0.085(-0.021-0.191) / 0.12
rs9926180 / A / 1418 / 3.1±0.87 / 2.96±0.82 / 3.08±0.85 / -0.041(-0.11-0.028) / 0.25
TG (mmol/L)b / rs1421085 / C / 561 / 1.2±0.84 / 1.19±0.79 / 1.2±0.8 / -0.009(-0.108-0.089) / 0.86
rs8050136 / A / 599 / 1.01±0.78 / 1.19±0.81 / 1.21±0.79 / -0.076(-0.173-0.021) / 0.13
rs9939609 / A / 1555 / 1.25±0.7 / 1.3±0.74 / 1.32±0.72 / -0.034(-0.088-0.02) / 0.21
rs9930506 / G / 595 / 1.06±0.8 / 1.19±0.82 / 1.26±0.76 / -0.1(-0.197--0.003) / 0.04
rs9926180 / A / 1418 / 1.44±0.7 / 1.24±0.69 / 1.35±0.7 / -0.026(-0.084-0.031) / 0.37
Blood Urea (mmol/L)b / rs1421085 / C / 458 / 9.26±4.41 / 8.95±4.04 / 8.98±4.05 / 0.104(-0.433-0.642) / 0.70
rs8050136 / A / 493 / 9.29±4.31 / 8.82±4.17 / 9.05±4.12 / 0.091(-0.454-0.636) / 0.74
rs9939609 / A / 1447 / 9.27±4.09 / 8.96±3.92 / 9.08±4.1 / 0.122(-0.169-0.412) / 0.41
rs9930506 / G / 491 / 8.9±4.44 / 8.93±4.14 / 9.15±4.12 / -0.006(-0.542-0.53) / 0.98
rs9926180 / A / 1311 / 9.12±3.61 / 8.95±4.07 / 9.2±4.06 / -0.089(-0.414-0.236) / 0.59
Uric acid (umol/L)b / rs1421085 / C / 458 / 358.6±87.88 / 325±97.47 / 329.6±89.53 / 3.777(-7.584-15.14) / 0.52
rs8050136 / A / 493 / 338.1±85.73 / 328.8±101 / 335.5±87.02 / -3.72(-14.97-7.527) / 0.52
rs9939609 / A / 1445 / 306.9±89.16 / 308±95.37 / 319.6±91.41 / -7.445(-13.73--1.164) / 0.02
rs9930506 / G / 491 / 332.1±97.78 / 329±96.15 / 337±88.79 / -1.762(-12.84-9.315) / 0.76
rs9926180 / A / 1310 / 312.6±87.88 / 308.1±94.68 / 306.6±93.76 / 2.408(-4.651-9.468) / 0.50
Creatinine (umol/L)b / rs1421085 / C / 458 / 89.55±53.02 / 69.6±52.54 / 73.87±49.51 / 4.009(-2.227-10.25) / 0.21
rs8050136 / A / 493 / 93.83±47.39 / 70.19±54.01 / 75.07±48.44 / 5.519(-0.654-11.69) / 0.08
rs9939609 / A / 1444 / 67.14±55.78 / 67.89±52.81 / 72.07±51.99 / -1.581(-4.967-1.805) / 0.36
rs9930506 / G / 491 / 84.39±56.8 / 72.02±50.54 / 74.98±49.19 / 6.686(0.698-12.67) / 0.03
rs9926180 / A / 1309 / 65.55±53.27 / 67.17±54 / 68.88±53.27 / -1.747(-5.511-2.016) / 0.36
Systolic BP (mmHg)b / rs1421085 / C / 642 / 126.9±15.32 / 127.8±16.44 / 125.9±17.77 / 0.965(-0.856-2.785) / 0.30
rs8050136 / A / 686 / 130.6±17.3 / 127.6±16.48 / 125.6±16.59 / 2.329(0.534-4.124) / 0.01
rs9939609 / A / 1512 / 129.2±15.93 / 128.2±16.18 / 128.3±17.49 / 0.711(-0.452-1.875) / 0.23
rs9930506 / G / 680 / 126.4±16.54 / 126.9±16.02 / 126.9±18.01 / 0.158(-1.61-1.926) / 0.86
rs9926180 / A / 1367 / 127.6±16.14 / 128.4±17.29 / 128.7±17.23 / 0.141(-1.209-1.491) / 0.84
Diasystolic BP (mmHg)b / rs1421085 / C / 642 / 83.19±8.23 / 83.24±8.88 / 82.88±9.15 / 0.127(-0.874-1.128) / 0.80
rs8050136 / A / 686 / 84.86±8.16 / 83.05±8.8 / 82.62±8.99 / 0.844(-0.153-1.841) / 0.10
rs9939609 / A / 1512 / 83.71±8.55 / 83.08±9.05 / 83.31±9.69 / 0.124(-0.554-0.803) / 0.72
rs9930506 / G / 680 / 83.01±8.62 / 83.11±8.46 / 82.89±9.54 / 0.131(-0.842-1.103) / 0.79
rs9926180 / A / 1367 / 84.24±8.95 / 83±9.52 / 83.3±9.53 / 0.254(-0.534-1.041) / 0.53

aAnalysis adjusted for sex and age

bAnalysis adjusted for sex, age and BMI

Supplementary Table 8: Association of variants with quantitative traits in combined study population

Triat / SNP / A1 / NMISS / Mean ± SD / β (95% CI) / P
aa / ab / bb
BMI (Kg/m2)a / rs1421085 / C / 1626 / 25.18±4.736 / 24.8±4.902 / 24.06±4.814 / 0.635(0.302-0.968) / 0.0002
rs8050136 / A / 1670 / 24.92±4.803 / 24.94±4.974 / 24.09±4.69 / 0.563(0.227-0.898) / 0.001
rs9939609 / A / 2626 / 25.23±4.921 / 25.22±4.79 / 24.71±4.807 / 0.322(0.057-0.587) / 0.02
rs9930506 / G / 1615 / 24.51±4.951 / 24.82±4.91 / 24.23±4.701 / 0.179(-0.148-0.506) / 0.28
rs9926180 / A / 2477 / 25.35±4.562 / 24.67±4.819 / 25.17±4.901 / -0.238(-0.54-0.063) / 0.12
Waist (cm)a / rs1421085 / C / 1570 / 90.24±11.39 / 88.63±11.43 / 87.16±11.54 / 1.516(0.707-2.326) / 0.00022
rs8050136 / A / 1608 / 89.2±11.66 / 88.99±11.67 / 87.33±11.3 / 1.255(0.433-2.077) / 0.003
rs9939609 / A / 2561 / 90.62±11.79 / 89.64±11.46 / 88.67±11.53 / 1.021(0.38-1.662) / 0.002
rs9930506 / G / 1555 / 88.86±11.98 / 88.8±11.52 / 87.28±11.32 / 0.927(0.133-1.722) / 0.02
rs9926180 / A / 2413 / 90.33±11.1 / 88.54±11.44 / 89.49±11.66 / -0.349(-1.075-0.377) / 0.35
WHRa / rs1421085 / C / 1546 / 0.93±0.078 / 0.925±0.081 / 0.92±0.079 / 0.005(0-0.01) / 0.08
rs8050136 / A / 1583 / 0.931±0.078 / 0.926±0.08 / 0.922±0.079 / 0.005(0-0.01) / 0.05
rs9939609 / A / 2536 / 0.924±0.08 / 0.924±0.083 / 0.919±0.084 / 0.004(0-0.008) / 0.03
rs9930506 / G / 1530 / 0.924±0.08 / 0.924±0.077 / 0.922±0.082 / 0.002(-0.002-0.007) / 0.33
rs9926180 / A / 2388 / 0.926±0.085 / 0.917±0.081 / 0.921±0.085 / -0.001(-0.006-0.003) / 0.59
FPG (mmol/l)b / rs1421085 / C / 1587 / 4.808±0.592 / 4.787±0.586 / 4.791±0.63 / -0.009(-0.051-0.033) / 0.67
rs8050136 / A / 1630 / 4.811±0.599 / 4.785±0.583 / 4.79±0.626 / -0.002(-0.044-0.04) / 0.93
rs9939609 / A / 2586 / 4.796±0.614 / 4.801±0.612 / 4.819±0.627 / -0.015(-0.05-0.02) / 0.39
rs9930506 / G / 1575 / 4.782±0.608 / 4.804±0.596 / 4.774±0.615 / 0.022(-0.019-0.063) / 0.30
rs9926180 / A / 2437 / 4.79±0.645 / 4.782±0.61 / 4.804±0.628 / 0.001(-0.038-0.041) / 0.94
2 hr. PPG (mmol/L)b / rs1421085 / C / 433 / 5.798±1.058 / 5.755±1.162 / 5.679±1.086 / 0.095(-0.051-0.24) / 0.20
rs8050136 / A / 457 / 5.91±1.116 / 5.749±1.133 / 5.664±1.076 / 0.077(-0.064-0.218) / 0.29
rs9939609 / A / 735 / 5.739±0.989 / 5.694±1.09 / 5.621±1.097 / 0.075(-0.04-0.19) / 0.20
rs9930506 / G / 443 / 5.886±1.045 / 5.741±1.122 / 5.626±1.09 / 0.087(-0.053-0.226) / 0.22
rs9926180 / A / 675 / 5.55±1.11 / 5.687±1.07 / 5.675±1.082 / -0.085(-0.214-0.043) / 0.19
HbA1C (%)b / rs1421085 / C / 1457 / 5.38±0.53 / 5.413±0.529 / 5.372±0.522 / 0.013(-0.02-0.045) / 0.45
rs8050136 / A / 1492 / 5.383±0.515 / 5.414±0.526 / 5.391±0.53 / 0.009(-0.024-0.042) / 0.60
rs9939609 / A / 2449 / 5.451±0.473 / 5.473±0.475 / 5.461±0.481 / 0.001(-0.023-0.026) / 0.92
rs9930506 / G / 1441 / 5.375±0.508 / 5.458±0.539 / 5.36±0.522 / 0.018(-0.013-0.05) / 0.26
rs9926180 / A / 2302 / 5.461±0.448 / 5.439±0.472 / 5.43±0.461 / 0.01(-0.017-0.038) / 0.46
FPI (pmol/L)b / rs1421085 / C / 898 / 42.86±52.42 / 47.5±48.28 / 44.83±50.16 / -1.449(-5.877-2.98) / 0.52
rs8050136 / A / 897 / 42.1±53.38 / 47.97±47.92 / 44.74±50.36 / -1.617(-6.13-2.897) / 0.48
rs9939609 / A / 1775 / 46.22±49.02 / 49.05±42.67 / 49.58±44.68 / -2.065(-4.852-0.722) / 0.15
rs9930506 / G / 856 / 44.48±55.11 / 49.99±48.22 / 43.53±48.29 / 0.817(-3.468-5.101) / 0.71
rs9926180 / A / 1799 / 51.4±45.28 / 48.5±44.27 / 49.17±44.47 / 1.506(-1.534-4.547) / 0.33
HOMA IRb / rs1421085 / C / 882 / 1.601±1.974 / 1.741±1.842 / 1.615±1.88 / -0.028(-0.197-0.141) / 0.75
rs8050136 / A / 881 / 1.571±2.011 / 1.762±1.828 / 1.613±1.889 / -0.033(-0.206-0.139) / 0.70
rs9939609 / A / 1758 / 1.692±1.867 / 1.786±1.659 / 1.816±1.738 / -0.081(-0.19-0.028) / 0.14
rs9930506 / G / 840 / 1.643±2.061 / 1.838±1.832 / 1.555±1.825 / 0.058(-0.105-0.222) / 0.48
rs9926180 / A / 1781 / 1.875±1.767 / 1.772±1.711 / 1.794±1.727 / 0.055(-0.063-0.173) / 0.36
C-peptide (nmol/L)b / rs1421085 / C / 891 / 0.567±0.369 / 0.619±0.326 / 0.594±0.347 / -- / --
rs8050136 / A / 891 / 0.545±0.371 / 0.627±0.328 / 0.593±0.345 / -- / --
rs9939609 / A / 1767 / 0.614±0.37 / 0.68±0.324 / 0.667±0.349 / -0.02(-0.041-0.002) / 0.07
rs9930506 / G / 846 / 0.567±0.368 / 0.611±0.324 / 0.6±0.347 / -- / --
rs9926180 / A / 1791 / 0.691±0.362 / 0.655±0.326 / 0.67±0.35 / 0.006(-0.017-0.03) / 0.60
hsCRP (mg/L)b / rs1421085 / C / 1310 / 2.183±1.853 / 2.142±2.024 / 2.173±2.06 / -0.059(-0.213-0.094) / 0.45
rs8050136 / A / 1343 / 2.224±1.807 / 2.175±2.059 / 2.153±2.065 / -0.013(-0.17-0.143) / 0.87
rs9939609 / A / 2216 / 2.358±1.947 / 2.214±2.087 / 2.201±2.031 / 0.02(-0.102-0.142) / 0.74
rs9930506 / G / 1294 / 2.143±1.928 / 2.27±2.074 / 2.163±2.037 / -0.002(-0.153-0.15) / 0.98
rs9926180 / A / 2072 / 2.347±2.018 / 2.11±2.095 / 2.207±2.031 / 0.028(-0.108-0.164) / 0.69
TC (mmol/L)b / rs1421085 / C / 1549 / 4.591±1.171 / 4.624±1.031 / 4.546±1.074 / 0.03(-0.047-0.106) / 0.44
rs8050136 / A / 1587 / 4.51±1.116 / 4.653±1.047 / 4.541±1.073 / 0.012(-0.065-0.089) / 0.76
rs9939609 / A / 2534 / 4.697±1.084 / 4.761±1.048 / 4.703±1.099 / 0.015(-0.045-0.076) / 0.62
rs9930506 / G / 1534 / 4.477±1.086 / 4.674±1.074 / 4.524±1.04 / -0.007(-0.082-0.067) / 0.85
rs9926180 / A / 2384 / 4.747±1.03 / 4.656±1.063 / 4.772±1.065 / -0.059(-0.127-0.008) / 0.08
HDL-C (mmol/L)b / rs1421085 / C / 1454 / 1.106±0.35 / 1.144±0.366 / 1.141±0.356 / -0.009(-0.035-0.017) / 0.48
rs8050136 / A / 1492 / 1.108±0.342 / 1.145±0.358 / 1.138±0.364 / -0.008(-0.034-0.018) / 0.54
rs9939609 / A / 2443 / 1.162±0.349 / 1.202±0.35 / 1.198±0.355 / -0.009(-0.028-0.01) / 0.36
rs9930506 / G / 1439 / 1.133±0.382 / 1.159±0.347 / 1.118±0.361 / 0.009(-0.016-0.034) / 0.47
rs9926180 / A / 2295 / 1.148±0.367 / 1.204±0.343 / 1.219±0.358 / -0.026(-0.048--0.004) / 0.02
LDL-C (mmol/L)b / rs1421085 / C / 1549 / 2.972±0.921 / 2.952±0.838 / 2.852±0.881 / 0.064(0.001-0.127) / 0.05
rs8050136 / A / 1587 / 2.92±0.898 / 2.976±0.843 / 2.844±0.884 / 0.057(-0.006-0.121) / 0.08
rs9939609 / A / 2544 / 2.997±0.851 / 2.997±0.837 / 2.935±0.893 / 0.039(-0.011-0.088) / 0.12
rs9930506 / G / 1534 / 2.841±0.901 / 2.986±0.85 / 2.841±0.868 / 0.015(-0.047-0.076) / 0.64
rs9926180 / A / 2396 / 3.003±0.824 / 2.933±0.867 / 2.999±0.849 / -0.027(-0.082-0.028) / 0.33
TG (mmol/L)b / rs1421085 / C / 1550 / 1.428±0.884 / 1.432±0.851 / 1.395±0.864 / 0.007(-0.054-0.067) / 0.82
rs8050136 / A / 1588 / 1.339±0.876 / 1.433±0.849 / 1.393±0.866 / -0.023(-0.084-0.038) / 0.46
rs9939609 / A / 2545 / 1.359±0.784 / 1.406±0.79 / 1.393±0.795 / -0.013(-0.058-0.031) / 0.56
rs9930506 / G / 1535 / 1.373±0.877 / 1.403±0.837 / 1.415±0.884 / -0.023(-0.082-0.036) / 0.44
rs9926180 / A / 2397 / 1.503±0.785 / 1.36±0.773 / 1.427±0.778 / -0.007(-0.057-0.042) / 0.77
Blood Urea (mmol/L)b / rs1421085 / C / 1391 / 9.092±3.398 / 8.912±3.47 / 8.821±3.362 / 0.14(-0.113-0.394) / 0.28
rs8050136 / A / 1426 / 9.04±3.314 / 8.876±3.552 / 8.86±3.413 / 0.091(-0.169-0.351) / 0.49
rs9939609 / A / 2380 / 9.125±3.627 / 8.945±3.642 / 8.955±3.694 / 0.098(-0.11-0.306) / 0.36
rs9930506 / G / 1374 / 8.963±3.432 / 8.863±3.584 / 8.954±3.354 / 0.017(-0.234-0.268) / 0.89
rs9926180 / A / 2233 / 8.936±3.338 / 8.853±3.687 / 9.089±3.656 / -0.105(-0.338-0.127) / 0.38
Uric acid (umol/L)b / rs1421085 / C / 1358 / 326.7±185.2 / 308.5±196.9 / 310.4±190.1 / 0.85(-12.83-14.53) / 0.90
rs8050136 / A / 1393 / 314.6±181.9 / 310.8±198.4 / 314.3±185.3 / -2.829(-16.51-10.85) / 0.69
rs9939609 / A / 2345 / 305.6±149.4 / 305.4±163.3 / 312.9±155.1 / -4.566(-13.35-4.215) / 0.31
rs9930506 / G / 1341 / 310.4±173.7 / 298.4±187.9 / 323.7±196.7 / -7.053(-20.08-5.974) / 0.29
rs9926180 / A / 2199 / 298.3±150.5 / 305.3±172.9 / 304.3±154.1 / -0.825(-10.87-9.217) / 0.87
Creatinine (umol/L)b / rs1421085 / C / 1345 / 88.69±135.6 / 71.02±133.7 / 77.16±135.7 / 2.627(-6.901-12.16) / 0.59
rs8050136 / A / 1380 / 88.4±137.2 / 72.44±133.8 / 76.76±131.8 / 4.364(-5.154-13.88) / 0.37
rs9939609 / A / 2331 / 74.26±110.8 / 70.15±108.1 / 74.26±107.5 / 0.45(-5.45-6.349) / 0.88
rs9930506 / G / 1328 / 87.64±141 / 70.21±128.4 / 73.34±132.9 / 9.066(0.017-18.11) / 0.05
rs9926180 / A / 2185 / 58.63±94.19 / 75.75±113.8 / 70.22±110.3 / 0.009(-6.708-6.726) / 1.00
Systolic BP (mmHg)b / rs1421085 / C / 1553 / 124.4±18.56 / 127.2±17.49 / 126.2±18.57 / -0.518(-1.761-0.725) / 0.41
rs8050136 / A / 1597 / 125.7±20 / 127.1±17.5 / 126±17.95 / -0.096(-1.348-1.155) / 0.88
rs9939609 / A / 2423 / 126.7±18.35 / 127.6±16.99 / 127.6±18.06 / -0.233(-1.205-0.739) / 0.64
rs9930506 / G / 1541 / 125.1±19.2 / 127±17.45 / 126.6±18.34 / -0.62(-1.829-0.59) / 0.32
rs9926180 / A / 2267 / 127±17.4 / 127±17.59 / 127.9±18.13 / -0.135(-1.253-0.984) / 0.81
Diasystolic BP (mmHg)b / rs1421085 / C / 1551 / 80.36±10.71 / 81.45±10.2 / 81.43±10.3 / -0.482(-1.205-0.242) / 0.19
rs8050136 / A / 1595 / 80.8±10.8 / 81.46±10.19 / 81.33±10.18 / -0.249(-0.978-0.48) / 0.50
rs9939609 / A / 2421 / 81.61±10.15 / 82.01±9.911 / 82.2±10.26 / -0.291(-0.863-0.281) / 0.32
rs9930506 / G / 1539 / 80.5±10.63 / 81.6±9.724 / 81.51±10.83 / -0.444(-1.147-0.259) / 0.22
rs9926180 / A / 2265 / 82.48±9.956 / 81.59±10.24 / 82.1±10.27 / -0.03(-0.69-0.629) / 0.93

aAnalysis adjusted for sex and age

bAnalysis adjusted for sex, age and BMI

Supplementary Table 9: Association of haplotypes (SNPs rs1421085, rs8050136 and rs9939609) with type 2 diabetes, BMI and obesity

Haplotypea / Type 2 diabetesb / BMI¶ / Obese + over weight vs. Normal weightc / Obese vs. Normal weightc / Overweight vs. Normal weightc
Freq.
cases / Freq.
controls / ORb / Pb / Freq. / βc / Pc / Freq.
OB+OW / Freq.
NW / ORb / Pb / Freq.
OB / Freq.
NW / ORc / Pc / Freq.
OW / Freq.
NW / ORc / Pc
CAA / 0.35 / 0.34 / 1.04 / 0.53 / 0.34 / 0.017 / 0.07 / 0.35 / 0.33 / 1.06 / 0.51 / 0.34 / 0.33 / 1.05 / 0.66 / 0.35 / 0.33 / 1.08 / 0.57
TCT / 0.62 / 0.64 / 0.94 / 0.32 / 0.64 / -0.016 / 0.07 / 0.64 / 0.65 / 0.95 / 0.54 / 0.64 / 0.65 / 0.96 / 0.68 / 0.63 / 0.65 / 0.94 / 0.60

aOnly haplotypes with frequency >0.10 in controls were analyzed

bAnalysis adjusted for sex, age and BMI

cAnalysis adjusted for sex and age

Supplementary Figure 1: Power of the present study (combined study) for various effect sizes for an allele frequency of 0.24

Supplementary Figure 2: Schematic view of pairwise linkage disequilibrium (LD) between the SNPs of FTO. (a) the pair wise LD (D' values) between the SNPs, (b) pair wise correlation (r2 values) between the SNPs

(a) D' plot(b) r2plot

1

Supplementary Figure 3: Multidimensional scaling

608 unlinked markers (r2<0.20) were used to obtain the positions on the first and second dimensions using PLINK for the samples of the initial phase.

1