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Supplementarydata
1.
SUPPLEMENTARY DATA Supplementary Table
1. General characteristics of Type 2 diabetes subjects by obesity status NON-OBESE OBESE Controls Cases Controls Cases 692 643 298 384 42.1% 42.1% 33.9% 25% *† 54(49-63) 55(46-63) * 52(48-59) 51(42-59.5) *† - 46(36-53) - 45(38-52) BMI (kg/m2) 26.2(24.527.7) 26.8(24.7-28.4) * 32.6(31.1-34.5) 32.9(31.4-36.1) *† Waist circumference (cm) 89.4(84-94) 94.1(88-101) * 103(97-110) 109(103.5-116.5) *† 120(110-130) 129(119-140) * 126(118-140) 130(120-145.5) *† Diastolic Blood Pressure (mmHg) 80(70-84) 80(70-90) * 82(76.5-90) 86(80-90.5) *† Glucose (mg/dL) 87(82-93) 226(148-318) * Total Cholesterol (mg/dL) 213(189-241) 198(174-238) * 210(187-241.5) 209.5(178-236.5) * Triglycerides (mg/dL) 153(112-226) 224(152-351) * 183(138.5257.5) 246(167-390) *† HDL (mg/dL) 44(38-53) 39(32-45) * 41(35-49) 37.5(30-44) * LDL (mg/dL) 134(114-159) 111(85-138) * 129(111-151) 112.5(87-139) * Individuals (n) Male (%) Age (years) Age at diagnosis (years) Systolic Blood Pressure (mmHg) 92(85-97) 213.5(147-306) * Median and percentiles 25 and 75 of baseline characteristics are shown. Statistically significant observations are bold- faced. *P< 0.05 comparisons between type 2 diabetes cases and controls. †P< 0.05 comparisons between non obese and obese type 2 diabetes cases. ©2012 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-0550/-/DC1
2.
SUPPLEMENTARY DATA Supplementary Table
2. Allele frequency distribution of 21 SNPs studied in Mexican Mestizos population and the comparison with Europeans Nearest Gene Chr SNP RA KCNJ11 PPARG TCF7L2 SLC30A8 11 3 10 8 HHEX 10 CDKN2A/2B CDKAL1 IGF2BP2 ARHGEF11 JAZF1 CDC123/ CAMK1D FTO TSPAN8/ LGR5 KCNQ1 ADAMTS9 NOTCH2 NXPH1 RORA UBQLNL RALGPS2 9 6 3 1 7 10 16 12 11 3 1 7 15 11 1 rs5219 rs1801282 rs7903146 rs13266634 rs1111875 rs7923837 rs10811661 rs7754840 rs4402960 rs945508 rs864745 rs12779790 rs8050136 rs7961581 rs2237892 rs4607103 rs10923931 rs757705 rs7164773 rs979752 rs2773080 T C T C C G T C T A T G A C C C T G T C A Controls 0.373 0.868 0.163 0.729 0.623 0.455 0.877 0.285 0.191 0.252 0.660 0.161 0.200 0.125 0.663 0.697 0.078 0.654 0.625 0.854 0.197 Total Cases 0.396 0.877 0.172 0.770 0.626 0.485 0.911 0.313 0.213 0.233 0.679 0.197 0.194 0.132 0.720 0.710 0.081 0.684 0.641 0.850 0.193 Early Onset 0.399 0.876 0.180 0.788 0.626 0.458 0.913 0.326 0.199 0.225 0.692 0.213 0.192 0.132 0.723 0.720 0.083 0.694 0.642 0.853 0.181 Risk Allele frequency Non obese Late Onset Controls Cases 0.393 0.374 0.408 0.877 0.866 0.875 0.163 0.170 0.171 0.752 0.726 0.769 0.626 0.620 0.621 0.512 0.452 0.500 0.909 0.880 0.912 0.300 0.275 0.326 0.227 0.197 0.213 0.241 0.259 0.217 0.666 0.661 0.687 0.182 0.161 0.202 0.197 0.190 0.182 0.132 0.133 0.139 0.717 0.669 0.721 0.701 0.688 0.706 0.079 0.081 0.079 0.674 0.658 0.689 0.639 0.627 0.647 0.847 0.848 0.855 0.205 0.199 0.196 Obese European* Controls Cases Controls Cases 0.371 0.375 0.464† 0.489‡ 0.872 0.879 0.823 0.848 0.149 0.172 0.181 0.227‡ 0.736 0.770 0.609† 0.649‡ 0.628 0.635 0.522† 0.546‡ 0.464 0.461 0.597† 0.622‡ 0.871 0.909 0.850† 0.872‡ 0.307 0.293 0.360† 0.387‡ 0.177 0.213 0.304† 0.341‡ 0.236 0.260 0.460† 0.660 0.666 0.501† 0.161 0.188 0.183 0.223 0.217 0.381† 0.406‡ 0.108 0.120 0.269† 0.650 0.719 0.930† 0.715 0.718 0.761† 0.073 0.084 0.106† 0.643 0.674 0.621 0.630 0.869 0.840 0.194 0.188 - Chr, Chromosome; RA, Risk Allele; defined as previously reported associated to T2D risk in other populations. * Risk allele frequencies reported in European population. † P<0.05 comparisons of risk allele frequencies between Mexican controls and European controls. ‡ Statistically significant differences between Mexican-Mestizo and European population type 2 diabetes cases. ©2012 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-0550/-/DC1
3.
SUPPLEMENTARY DATA Supplementary Table
3. Comparison of the effect sizes in Mexicans vs. European populations. OR (95% CI) p-value OR (95% CI) Heterogeneity Test TCF7L2 1.39(1.04-1.85) 0.024 1.37(1.31-1.43) 0.92 rs13266634 SLC30A8 1.22(1.05-1.41) 0.009 1.12(1.07-1.16) 0.26 rs7923837 HHEX 1.21(1.02-1.44) 0.025 1.22(1.01-1.43) 0.95 rs10811661 CDKN2A/2B 1.42(1.15-1.75) 0.001 1.20(1.14-1.25) 0.12 rs7754840 CDKAL1 1.25(1.06-1.49) 0.009 1.12(1.08-1.16) 0.23 rs4402960 IGF2BP2 1.24 (1.01-1.53) 0.042 1.14(1.11-1.18) 0.44 1.24(1.05-1.47) 0.013 1.11(1.07-1.14) 0.21 1.36(1.13-1.64) 0.001 1.42 (1.34–1.49) 1.43(1.34-1.52)* 0.62 0.66 SNP rs7903146 Mexican Mestizos Nearest Gene rs12779790 CDC123/CAMK1D rs2237892 KCNQ1 Reported in Europeans Odds ratios in Mexican and European populations are shown. * Odds ratio reported in Asians. Supplementary Table 4. Ancestry Informative Markers (AIMs) used in the study. dbSNP RS ID Number rs2817611 rs6684063 rs1934393 rs3768176 rs3828121 rs3806218 rs2592888 rs4657449 rs7535375 rs1073319 rs1470524 rs842634 rs10515919 rs4852696 rs3860446 rs1036543 rs2711070 rs868179 rs10497705 rs1517634 rs10498255 rs304051 rs1498991 rs9310888 Chromosome 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 2 2 3 3 3 Physical Location 11322709 30201812 48578535 56937923 81844793 144518860 156802365 162652658 232954308 29414989 45104050 61065756 75515133 83126181 104110751 133886983 159705078 177752041 190694557 224386024 231814769 4553306 20875097 29261727 Delta_Af_Eu 0.675 0.611 0.620 0.044 0.131 0.608 0.674 0.012 0.603 0.107 0.563 0.234 0.020 0.655 0.615 0.726 0.325 0.627 0.120 0.000 0.560 0.202 0.032 0.592 Delta_Af_NA 0.689 0.056 0.078 0.739 0.700 0.763 0.912 0.650 0.689 0.750 0.311 0.739 0.694 0.450 0.028 0.017 0.828 0.700 0.749 0.833 0.717 0.750 0.694 0.667 Delta_Eu_NA 0.014 0.667 0.542 0.695 0.569 0.155 0.238 0.662 0.086 0.643 0.252 0.505 0.714 0.205 0.643 0.743 0.502 0.073 0.629 0.833 0.157 0.548 0.726 0.075 ©2012 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-0550/-/DC1
4.
SUPPLEMENTARY DATA rs10510791 rs1395771 rs1919550 rs2035573 rs1984473 rs6804094 rs1398829 rs719776 rs10517518 rs9307613 rs10519979 rs10520440 rs257748 rs1353251 rs9292118 rs6883095 rs153898 rs1990745 rs10515535 rs1477277 rs6911727 rs10484578 rs993314 rs9320808 rs6569792 rs9295316 rs10486576 rs10248051 rs10214949 rs10488172 rs802524 rs9325872 rs7463344 rs4130405 rs1898280 rs4733652 rs2840290 rs4013967 rs10491654 rs10508349 rs2785279 rs4934436 rs1397618 rs2595456 rs948360 rs10501474 rs567992 rs879780 3 3 3 3 3 3 4 4 4 4 4 4 5 5 5 5 5 5 5 5 6 6 6 6 6 6 7 7 7 7 7 8 8 8 8 8 9 9 9 10 10 10 10 11 11 11 11 11 57251433 97784481 122685074 132534415 157132197 188378883 21774158 33583840 61798796 130816225 150212578 181494895 15872353 35902708 55916081 79975120 94262695 103458138 143544652 180784684 9061397 35293174 73434170 121635172 132675321 158476352 27861415 50861102 78660644 132751390 145343383 20490544 33921195 99377358 116031043 129801116 16723957 72354189 97519365 8302970 33713882 90447897 120497262 6849072 65882085 80126955 105800114 129545756 0.484 0.632 0.004 0.317 0.575 0.318 0.754 0.774 0.087 0.681 0.285 0.214 0.425 0.175 0.657 0.313 0.655 0.119 0.714 0.655 0.337 0.569 0.733 0.766 0.567 0.068 0.044 0.750 0.564 0.187 0.651 0.623 0.639 0.190 0.651 0.155 0.593 0.596 0.214 0.044 0.562 0.242 0.658 0.218 0.724 0.587 0.155 0.619 0.839 0.090 0.806 0.839 0.911 0.839 0.778 0.750 0.811 0.740 0.800 0.833 0.161 0.706 0.790 0.828 0.050 0.767 0.867 0.700 0.861 0.878 0.200 0.106 0.689 0.837 0.744 0.117 0.685 0.772 0.689 0.056 0.639 0.800 0.056 0.817 0.039 0.941 0.400 0.711 0.757 0.272 0.706 0.306 0.750 0.744 0.667 0.667 0.354 0.543 0.810 0.521 0.336 0.521 0.024 0.024 0.724 0.058 0.515 0.619 0.586 0.531 0.133 0.514 0.705 0.648 0.152 0.045 0.524 0.308 0.533 0.871 0.121 0.769 0.700 0.633 0.121 0.586 0.038 0.679 0.000 0.610 0.595 0.662 0.632 0.345 0.614 0.755 0.195 0.514 0.048 0.524 0.026 0.157 0.512 0.048 ©2012 American
Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-0550/-/DC1
5.
SUPPLEMENTARY DATA rs4625554 rs4762106 rs10506816 rs249847 rs4076700 rs4034627 rs2585901 rs10507688 rs5000507 rs10492585 rs9323178 rs1451928 rs2296274 rs10131076 rs9302185 rs10520678 rs30125 rs1004704 rs10500505 rs4130513 rs10491097 rs1990743 rs2253624 rs1013459 rs2042762 rs12953952 rs888861 rs708915 rs2208139 rs354747 rs2829454 rs138022 12 12 12 12 12 12 13 13 13 13 14 14 14 14 15 15 16 16 16 16 17 17 17 18 18 18 19 20 20 20 21 22 4286565 64304740 78427325 97370184 115795273 126750571 19218271 61204229 79886955 103084177 21103774 46330779 59907219 78764426 52670920 86667051 14321100 48315382 64718164 78238277 19523240 64494057 70329204 11690534 33529609 65886896 40073692 8395667 38594383 59598070 25194942 38856075 0.131 0.710 0.861 0.408 0.627 0.734 0.089 0.167 0.574 0.840 0.276 0.004 0.632 0.623 0.685 0.578 0.590 0.187 0.159 0.639 0.592 0.005 0.824 0.667 0.000 0.788 0.738 0.635 0.167 0.560 0.218 0.571 0.700 0.139 0.761 0.911 0.694 0.748 0.698 0.733 0.861 0.900 0.790 0.661 0.849 0.694 0.842 0.846 0.539 0.839 0.744 0.530 0.078 0.572 0.824 0.733 0.733 0.828 0.900 0.002 0.800 0.683 0.878 0.800 0.569 0.571 0.100 0.503 0.067 0.014 0.787 0.567 0.288 0.060 0.514 0.657 0.217 0.071 0.157 0.268 0.051 0.652 0.586 0.109 0.514 0.567 0.000 0.067 0.733 0.040 0.162 0.633 0.633 0.124 0.660 0.229 Delta_Af_Eu -
Difference in allele frequency between Africans and Europeans; Delta_Af_NA Difference in allele frequency between Africans and Native Americans; Delta_Eu_NA - Difference in allele frequency between Europeans and Native Americans . ©2012 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-0550/-/DC1
6.
SUPPLEMENTARY DATA Supplementary Table
5. Allele frequency distribution of the 3 SNPs not considered in the association analysis. Nearest Gene Chr SNP RA CDKAL1 IGF2BP2 THADA 6 3 2 rs10484634† rs1470579‡ rs7578597† T C T Controls 0.974 0.190 0.959 Total Cases 0.980 0.213 0.964 Early Onset 0.978 0.203 0.971 Risk Allele frequency Non obese Obese European* Late Onset Controls Cases Controls Cases Controls Cases 0.980 0.979 0.980 0.964 0.980 0.222 0.192 0.213 0.185 0.213 0.30 0.32 0.957 0.958 0.963 0.961 0.965 0.90 - Chr, Chromosome; RA, Risk Allele; defined as previously reported associated to T2D risk in other populations. * Risk allele frequencies reported in European population. †SNPs with a minor allele frequency < 0.05. ‡SNP is not in Hardy–Weinberg equilibrium in control group (p=0.002). ©2012 American Diabetes Association. Published online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db11-0550/-/DC1
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