Supplementary Table 1. All SNPs with p < 10-5 for GGT in either the adult or adolescent data.
Adults / AdolescentsSNP / Chr. / HapMap bp / beta / se / rank / P / beta / se / rank / P
rs1497406 / 1 / 16,377,907 / 0.084 / 0.016 / 50 / 2.50E-07 / 0.056 / 0.031 / # / 0.077
rs4669892 / 2 / 12,915,014 / 0.243 / 0.052 / 79 / 2.90E-06 / 0.020 / 0.117 / # / 0.86
rs11689205 / 2 / 23,136,276 / -0.192 / 0.038 / 53 / 4.30E-07 / 0.069 / 0.077 / # / 0.37
rs2540914 / 2 / 60,463,915 / 0.076 / 0.016 / 83 / 3.40E-06 / -0.026 / 0.032 / # / 0.43
rs243074 / 2 / 60,471,265 / 0.080 / 0.016 / 56 / 5.80E-07 / -0.040 / 0.032 / # / 0.20
rs243073 / 2 / 60,472,194 / 0.074 / 0.017 / 115 / 8.10E-06 / -0.026 / 0.033 / # / 0.43
rs243072 / 2 / 60,472,300 / 0.080 / 0.016 / 57 / 7.20E-07 / -0.039 / 0.032 / # / 0.21
rs243071 / 2 / 60,472,532 / 0.080 / 0.016 / 58 / 7.20E-07 / -0.039 / 0.032 / # / 0.21
rs243069 / 2 / 60,474,338 / 0.075 / 0.017 / 101 / 6.20E-06 / -0.025 / 0.033 / # / 0.45
rs184839 / 2 / 60,478,904 / 0.079 / 0.016 / 59 / 7.80E-07 / -0.039 / 0.032 / # / 0.21
rs2042839 / 2 / 231,151,811 / 0.013 / 0.022 / # / 0.55 / -0.186 / 0.042 / 23 / 9.30E-06
rs6553202 / 4 / 189,686,663 / 0.076 / 0.017 / 116 / 8.10E-06 / -0.033 / 0.032 / # / 0.30
rs17283752 / 5 / 92,277,837 / -0.030 / 0.043 / # / 0.49 / 0.394 / 0.086 / 12 / 4.10E-06
rs17166656 / 5 / 98,456,063 / 0.063 / 0.039 / # / 0.102 / -0.331 / 0.074 / 18 / 8.70E-06
rs17166666 / 5 / 98,463,458 / 0.063 / 0.039 / # / 0.102 / -0.331 / 0.074 / 19 / 8.70E-06
rs7720227 / 5 / 98,468,720 / 0.063 / 0.039 / # / 0.102 / -0.331 / 0.074 / 20 / 8.70E-06
rs7715722 / 5 / 98,468,884 / 0.063 / 0.039 / # / 0.102 / -0.331 / 0.074 / 21 / 8.70E-06
rs9649011 / 7 / 124,989,908 / -0.074 / 0.016 / 94 / 4.70E-06 / 0.003 / 0.032 / # / 0.91
rs2694006 / 7 / 124,990,439 / -0.078 / 0.016 / 64 / 1.70E-06 / -0.005 / 0.032 / # / 0.87
rs792416 / 7 / 124,991,175 / -0.075 / 0.016 / 92 / 4.50E-06 / 0.003 / 0.032 / # / 0.93
rs792160 / 7 / 125,002,045 / -0.078 / 0.016 / 65 / 1.70E-06 / -0.005 / 0.032 / # / 0.87
rs792162 / 7 / 125,004,164 / -0.084 / 0.017 / 55 / 5.50E-07 / -0.017 / 0.033 / # / 0.61
rs6965493 / 7 / 125,005,440 / -0.075 / 0.016 / 88 / 4.40E-06 / 0.004 / 0.032 / # / 0.90
rs1123461 / 7 / 125,006,438 / -0.075 / 0.016 / 89 / 4.40E-06 / 0.004 / 0.032 / # / 0.90
rs813781 / 7 / 125,006,473 / -0.078 / 0.016 / 66 / 1.70E-06 / -0.005 / 0.032 / # / 0.87
rs1833082 / 7 / 125,007,140 / -0.078 / 0.016 / 67 / 1.70E-06 / -0.005 / 0.032 / # / 0.87
rs1833083 / 7 / 125,007,189 / -0.078 / 0.016 / 68 / 1.70E-06 / -0.005 / 0.032 / # / 0.87
rs3857841 / 7 / 125,011,838 / -0.075 / 0.016 / 90 / 4.40E-06 / 0.004 / 0.032 / # / 0.90
rs792191 / 7 / 125,013,128 / -0.078 / 0.016 / 69 / 1.70E-06 / -0.005 / 0.032 / # / 0.87
rs792196 / 7 / 125,015,369 / -0.078 / 0.016 / 70 / 1.70E-06 / -0.005 / 0.032 / # / 0.87
rs792197 / 7 / 125,015,530 / -0.077 / 0.016 / 76 / 2.30E-06 / -0.001 / 0.032 / # / 0.97
rs10954077 / 7 / 125,017,678 / -0.077 / 0.016 / 77 / 2.30E-06 / -0.001 / 0.032 / # / 0.97
rs2524888 / 7 / 125,021,343 / -0.078 / 0.016 / 71 / 1.70E-06 / -0.005 / 0.032 / # / 0.87
rs986278 / 7 / 125,022,301 / -0.078 / 0.016 / 72 / 1.70E-06 / -0.004 / 0.032 / # / 0.90
rs9649481 / 7 / 125,024,810 / -0.078 / 0.016 / 73 / 1.70E-06 / -0.004 / 0.032 / # / 0.90
rs3847096 / 7 / 125,026,294 / -0.071 / 0.016 / 118 / 8.40E-06 / 0.000 / 0.031 / # / 0.99
rs4731254 / 7 / 125,027,629 / -0.075 / 0.016 / 81 / 3.30E-06 / -0.010 / 0.031 / # / 0.76
rs792177 / 7 / 125,028,367 / -0.075 / 0.016 / 82 / 3.30E-06 / -0.010 / 0.031 / # / 0.76
rs792180 / 7 / 125,028,765 / -0.075 / 0.016 / 84 / 3.40E-06 / -0.010 / 0.031 / # / 0.75
rs7793003 / 7 / 125,031,904 / -0.072 / 0.016 / 102 / 6.80E-06 / -0.001 / 0.031 / # / 0.97
rs2040752 / 7 / 125,032,420 / -0.072 / 0.016 / 103 / 6.80E-06 / -0.001 / 0.031 / # / 0.97
rs1419702 / 7 / 125,032,634 / -0.072 / 0.016 / 104 / 6.80E-06 / -0.001 / 0.031 / # / 0.97
rs1419703 / 7 / 125,032,654 / -0.072 / 0.016 / 105 / 6.80E-06 / -0.001 / 0.031 / # / 0.97
rs1859261 / 7 / 125,034,207 / -0.072 / 0.016 / 111 / 7.40E-06 / -0.001 / 0.031 / # / 0.97
rs996867 / 7 / 125,034,557 / -0.072 / 0.016 / 112 / 7.40E-06 / -0.001 / 0.031 / # / 0.97
rs983849 / 7 / 125,035,822 / -0.072 / 0.016 / 108 / 7.20E-06 / 0.000 / 0.031 / # / 0.99
rs1419698 / 7 / 125,036,674 / -0.072 / 0.016 / 113 / 7.40E-06 / -0.001 / 0.031 / # / 0.97
rs1579222 / 7 / 125,039,007 / -0.072 / 0.016 / 114 / 7.50E-06 / -0.002 / 0.031 / # / 0.94
rs1419699 / 7 / 125,049,164 / -0.073 / 0.016 / 97 / 5.50E-06 / -0.017 / 0.031 / # / 0.58
rs1160839 / 7 / 125,051,537 / -0.074 / 0.016 / 85 / 3.50E-06 / 0.009 / 0.031 / # / 0.77
rs10954078 / 7 / 125,053,219 / -0.073 / 0.016 / 98 / 5.50E-06 / -0.017 / 0.031 / # / 0.58
rs10234626 / 7 / 125,053,414 / -0.073 / 0.016 / 99 / 5.50E-06 / -0.017 / 0.031 / # / 0.58
rs2189416 / 7 / 125,054,864 / -0.072 / 0.016 / 106 / 7.10E-06 / 0.001 / 0.031 / # / 0.96
rs2189417 / 7 / 125,054,938 / -0.072 / 0.016 / 107 / 7.10E-06 / 0.001 / 0.031 / # / 0.96
rs1158631 / 7 / 125,057,851 / -0.071 / 0.016 / 117 / 8.10E-06 / 0.004 / 0.031 / # / 0.90
rs12530516 / 7 / 125,062,994 / -0.072 / 0.016 / 110 / 7.30E-06 / 0.004 / 0.031 / # / 0.89
rs10278107 / 7 / 125,065,431 / -0.071 / 0.016 / 128 / 9.50E-06 / -0.008 / 0.031 / # / 0.78
rs2107113 / 7 / 125,068,605 / -0.071 / 0.016 / 125 / 8.80E-06 / 0.003 / 0.031 / # / 0.91
rs16935327 / 8 / 70,055,645 / -0.098 / 0.021 / 95 / 4.70E-06 / 0.042 / 0.041 / # / 0.31
rs10818541 / 9 / 99,966,982 / -0.080 / 0.018 / 91 / 4.40E-06 / 0.075 / 0.034 / # / 0.027
rs10985257 / 9 / 99,967,076 / -0.086 / 0.019 / 87 / 3.70E-06 / 0.045 / 0.036 / # / 0.21
rs4610873 / 9 / 99,973,854 / -0.078 / 0.017 / 80 / 2.90E-06 / 0.053 / 0.032 / # / 0.097
rs7850952 / 9 / 118,240,668 / -0.081 / 0.018 / 130 / 9.90E-06 / 0.048 / 0.036 / # / 0.180
rs11024031 / 11 / 16,729,166 / -0.014 / 0.016 / # / 0.39 / 0.138 / 0.031 / 25 / 9.90E-06
rs4757430 / 11 / 16,732,438 / -0.014 / 0.016 / # / 0.39 / 0.138 / 0.031 / 26 / 9.90E-06
rs11031734 / 11 / 32,324,311 / -0.086 / 0.018 / 86 / 3.60E-06 / -0.021 / 0.036 / # / 0.56
rs7103098 / 11 / 32,332,013 / -0.095 / 0.019 / 51 / 2.90E-07 / -0.059 / 0.036 / # / 0.096
rs12285677 / 11 / 32,338,743 / -0.096 / 0.019 / 49 / 2.40E-07 / -0.057 / 0.036 / # / 0.110
rs17788257 / 11 / 45,370,385 / 0.383 / 0.081 / 78 / 2.50E-06 / 0.153 / 0.150 / # / 0.31
rs2649999 / 12 / 119,864,927 / 0.098 / 0.017 / 44 / 1.00E-08 / 0.156 / 0.033 / 4 / 1.70E-06
rs2650000 / 12 / 119,873,345 / 0.107 / 0.017 / 38 / 3.40E-10 / 0.161 / 0.032 / 1 / 6.50E-07
rs7953249 / 12 / 119,888,107 / 0.091 / 0.016 / 45 / 3.30E-08 / 0.143 / 0.031 / 10 / 3.70E-06
rs2251468 / 12 / 119,889,509 / 0.107 / 0.017 / 39 / 3.40E-10 / 0.161 / 0.032 / 2 / 6.50E-07
rs10774579 / 12 / 119,889,593 / -0.081 / 0.016 / 54 / 4.90E-07 / -0.125 / 0.031 / 235 / 5.60E-05
rs1169288 / 12 / 119,901,033 / 0.126 / 0.017 / 6 / 4.30E-13 / 0.155 / 0.033 / 6 / 2.20E-06
rs2244608 / 12 / 119,901,371 / 0.125 / 0.017 / 7 / 4.80E-13 / 0.155 / 0.033 / 7 / 2.20E-06
rs1169286 / 12 / 119,903,439 / 0.102 / 0.016 / 37 / 3.30E-10 / 0.132 / 0.032 / 132 / 3.00E-05
rs7979473 / 12 / 119,904,643 / 0.106 / 0.017 / 34 / 1.70E-10 / 0.141 / 0.032 / 15 / 7.80E-06
rs7979478 / 12 / 119,904,646 / 0.106 / 0.017 / 36 / 2.40E-10 / 0.140 / 0.032 / 16 / 8.50E-06
rs1183910 / 12 / 119,905,190 / 0.124 / 0.017 / 8 / 1.10E-12 / 0.160 / 0.033 / 3 / 1.20E-06
rs11065385 / 12 / 119,907,769 / 0.123 / 0.017 / 9 / 1.30E-12 / 0.152 / 0.033 / 11 / 3.90E-06
rs2393791 / 12 / 119,908,339 / 0.106 / 0.017 / 35 / 2.20E-10 / 0.140 / 0.032 / 17 / 8.50E-06
rs2393775 / 12 / 119,908,957 / 0.110 / 0.017 / 31 / 4.60E-11 / 0.139 / 0.032 / 27 / 9.90E-06
rs7310409 / 12 / 119,909,244 / 0.111 / 0.017 / 29 / 3.20E-11 / 0.139 / 0.032 / 28 / 9.90E-06
rs1169300 / 12 / 119,915,608 / 0.133 / 0.018 / 4 / 6.00E-14 / 0.144 / 0.033 / 56 / 1.60E-05
rs1169302 / 12 / 119,916,685 / 0.088 / 0.016 / 46 / 6.20E-08 / 0.124 / 0.031 / 236 / 5.70E-05
rs2259820 / 12 / 119,919,725 / 0.134 / 0.018 / 1 / 5.50E-14 / 0.145 / 0.033 / 46 / 1.40E-05
rs2464196 / 12 / 119,919,810 / 0.134 / 0.018 / 2 / 5.50E-14 / 0.145 / 0.033 / 47 / 1.40E-05
rs2464195 / 12 / 119,919,858 / 0.119 / 0.017 / 12 / 4.20E-12 / 0.120 / 0.032 / 550 / 0.00017
rs2259816 / 12 / 119,919,970 / 0.119 / 0.017 / 13 / 4.20E-12 / 0.120 / 0.032 / 551 / 0.00017
rs1169303 / 12 / 119,920,759 / 0.082 / 0.016 / 52 / 4.00E-07 / 0.113 / 0.030 / 646 / 0.0002
rs1169306 / 12 / 119,922,694 / 0.118 / 0.017 / 11 / 3.80E-12 / 0.118 / 0.032 / 647 / 0.0002
rs1169307 / 12 / 119,922,765 / -0.079 / 0.017 / 74 / 2.00E-06 / -0.107 / 0.031 / 1747 / 0.00062
rs735396 / 12 / 119,923,227 / 0.119 / 0.017 / 14 / 4.20E-12 / 0.120 / 0.032 / 552 / 0.00017
rs1169310 / 12 / 119,923,816 / 0.119 / 0.017 / 15 / 4.20E-12 / 0.120 / 0.032 / 553 / 0.00017
rs1169312 / 12 / 119,925,844 / 0.119 / 0.017 / 16 / 4.20E-12 / 0.120 / 0.032 / 554 / 0.00017
rs1169313 / 12 / 119,927,053 / 0.119 / 0.017 / 17 / 4.20E-12 / 0.120 / 0.032 / 555 / 0.00017
rs2257764 / 12 / 119,930,829 / 0.134 / 0.018 / 3 / 5.50E-14 / 0.145 / 0.033 / 48 / 1.40E-05
rs2258287 / 12 / 119,938,696 / 0.115 / 0.017 / 30 / 4.30E-11 / 0.152 / 0.033 / 9 / 3.40E-06
rs1182933 / 12 / 119,939,005 / 0.133 / 0.018 / 5 / 6.80E-14 / 0.145 / 0.033 / 49 / 1.40E-05
rs2259693 / 12 / 119,942,378 / 0.095 / 0.016 / 43 / 4.40E-09 / 0.110 / 0.031 / 1045 / 0.00036
rs2259883 / 12 / 119,946,522 / -0.080 / 0.016 / 60 / 8.30E-07 / -0.103 / 0.031 / 2083 / 0.00074
rs2260399 / 12 / 119,954,036 / 0.095 / 0.016 / 42 / 3.70E-09 / 0.112 / 0.031 / 832 / 0.00027
rs10849829 / 12 / 119,954,639 / 0.096 / 0.016 / 41 / 3.60E-09 / 0.112 / 0.031 / 833 / 0.00027
rs3213545 / 12 / 119,955,720 / 0.125 / 0.018 / 10 / 1.50E-12 / 0.133 / 0.033 / 258 / 6.40E-05
rs8017161 / 14 / 102,632,948 / -0.087 / 0.017 / 48 / 1.90E-07 / -0.086 / 0.032 / 18635 / 0.0072
rs2297067 / 14 / 102,636,538 / -0.129 / 0.020 / 33 / 7.50E-11 / -0.099 / 0.038 / 24423 / 0.0096
rs10131298 / 14 / 102,638,367 / -0.127 / 0.020 / 40 / 3.70E-10 / -0.107 / 0.039 / 16522 / 0.0063
rs944002 / 14 / 102,642,568 / -0.135 / 0.020 / 21 / 1.50E-11 / -0.105 / 0.039 / 16772 / 0.0064
rs12902840 / 15 / 29,140,275 / -0.117 / 0.026 / 93 / 4.50E-06 / 0.112 / 0.052 / # / 0.031
rs3784600 / 15 / 29,146,844 / -0.115 / 0.026 / 109 / 7.20E-06 / 0.089 / 0.053 / # / 0.092
rs340005 / 15 / 58,665,322 / 0.080 / 0.017 / 61 / 1.30E-06 / 0.097 / 0.032 / 6000 / 0.0022
rs339969 / 15 / 58,670,573 / 0.080 / 0.017 / 62 / 1.30E-06 / 0.097 / 0.032 / 6001 / 0.0022
rs340029 / 15 / 58,682,257 / 0.079 / 0.017 / 75 / 2.10E-06 / 0.097 / 0.032 / 6248 / 0.0023
rs11630109 / 15 / 78,817,950 / -0.287 / 0.064 / 124 / 8.60E-06 / -0.004 / 0.127 / # / 0.97
rs11630693 / 15 / 78,843,401 / -0.287 / 0.064 / 126 / 8.80E-06 / -0.004 / 0.127 / # / 0.97
rs9790 / 16 / 3,526,231 / -0.090 / 0.020 / 131 / 1.00E-05 / -0.030 / 0.039 / # / 0.44
rs12596890 / 16 / 3,528,069 / -0.090 / 0.020 / 127 / 9.20E-06 / -0.031 / 0.038 / # / 0.42
rs12452019 / 17 / 48,720,687 / -0.002 / 0.016 / # / 0.92 / -0.140 / 0.031 / 14 / 6.40E-06
rs4968681 / 17 / 59,423,885 / -0.019 / 0.017 / # / 0.26 / -0.144 / 0.032 / 24 / 9.60E-06
rs9907593 / 17 / 59,426,369 / -0.017 / 0.017 / # / 0.30 / -0.144 / 0.032 / 22 / 8.90E-06
rs1078334 / 17 / 78,477,536 / 0.009 / 0.017 / # / 0.61 / -0.149 / 0.033 / 13 / 4.70E-06
rs729124 / 17 / 78,480,495 / 0.008 / 0.017 / # / 0.66 / -0.160 / 0.034 / 5 / 2.00E-06
rs4503880 / 18 / 54,235,034 / -0.090 / 0.020 / 96 / 4.90E-06 / -0.049 / 0.040 / # / 0.21
rs12373325 / 18 / 54,238,628 / -0.086 / 0.019 / 119 / 8.40E-06 / -0.034 / 0.039 / # / 0.39
rs4998040 / 18 / 54,244,979 / -0.086 / 0.019 / 120 / 8.40E-06 / -0.034 / 0.039 / # / 0.39
rs10871755 / 18 / 54,245,763 / -0.086 / 0.019 / 121 / 8.40E-06 / -0.034 / 0.039 / # / 0.39
rs7227231 / 18 / 54,245,865 / -0.086 / 0.019 / 122 / 8.40E-06 / -0.034 / 0.039 / # / 0.39
rs4245267 / 18 / 54,247,194 / -0.086 / 0.019 / 123 / 8.40E-06 / -0.034 / 0.039 / # / 0.39
rs6031595 / 20 / 42,488,074 / 0.078 / 0.016 / 63 / 1.60E-06 / -0.008 / 0.031 / # / 0.80
rs6031596 / 20 / 42,488,285 / 0.074 / 0.016 / 100 / 5.70E-06 / -0.013 / 0.031 / # / 0.68
rs5760485 / 22 / 23,316,473 / -0.119 / 0.018 / 27 / 2.70E-11 / 0.146 / 0.034 / 50 / 1.40E-05
rs2154611 / 22 / 23,319,920 / -0.116 / 0.018 / 32 / 6.00E-11 / 0.146 / 0.034 / 51 / 1.40E-05
rs4820599 / 22 / 23,320,213 / -0.119 / 0.018 / 25 / 2.50E-11 / 0.146 / 0.034 / 52 / 1.40E-05
rs2070477 / 22 / 23,320,916 / -0.121 / 0.018 / 22 / 1.50E-11 / 0.140 / 0.034 / 156 / 3.40E-05
rs6519519 / 22 / 23,321,863 / -0.121 / 0.018 / 23 / 1.50E-11 / 0.140 / 0.034 / 157 / 3.40E-05
rs6519520 / 22 / 23,321,895 / -0.119 / 0.018 / 26 / 2.50E-11 / 0.146 / 0.034 / 53 / 1.40E-05
rs5751901 / 22 / 23,322,266 / -0.117 / 0.017 / 18 / 8.70E-12 / 0.105 / 0.033 / 4165 / 1.50E-03
rs5760492 / 22 / 23,325,202 / -0.117 / 0.017 / 19 / 1.00E-11 / 0.107 / 0.033 / 3521 / 1.28E-03
rs2330795 / 22 / 23,326,582 / -0.117 / 0.017 / 20 / 1.00E-11 / 0.107 / 0.033 / 3522 / 1.28E-03
rs2017869 / 22 / 23,327,309 / -0.114 / 0.017 / 28 / 2.80E-11 / 0.112 / 0.033 / 2031 / 7.20E-04
rs2073398 / 22 / 23,329,104 / -0.116 / 0.017 / 24 / 1.60E-11 / 0.105 / 0.033 / 3857 / 1.43E-03
rs2001180 / 22 / 23,334,206 / -0.093 / 0.017 / 47 / 8.90E-08 / 0.120 / 0.034 / 1181 / 4.20E-04
rs5751933 / 22 / 23,412,586 / 0.006 / 0.016 / # / 0.69 / 0.146 / 0.031 / 8 / 3.10E-06
rs17661237 / 22 / 23,416,816 / 0.114 / 0.026 / 129 / 9.70E-06 / -0.067 / 0.050 / # / 0.180
Page 1 of 19
Supplementary Table 2. Results of gene-based analysis, showing all genes with p < 10-4 for GGT in combined adult and adolescent data.
Rank / Chr / Gene / Start / Stop / Pvalue1 / 12 / C12orf43 / 119,925,230 / 119,938,683 / Less than 10-6
2 / 12 / HNF1A / 119,900,931 / 119,924,697 / Less than 10-6
3 / 12 / OASL / 119,942,477 / 119,961,163 / Less than 10-6
4 / 22 / C22orf36 / 23,311,590 / 23,319,035 / Less than 10-6
5 / 22 / GGT1 / 23,309,717 / 23,354,972 / 1.00E-06
6 / 14 / C14orf73 / 102,636,233 / 102,646,647 / 2.00E-06
7 / 22 / SNRPD3 / 23,281,617 / 23,298,509 / 4.00E-06
8 / 22 / C22orf13 / 23,266,407 / 23,281,275 / 7.00E-06
9 / 1 / EPHA2 / 16,323,418 / 16,355,151 / 1.10E-05
10 / 14 / TNFAIP2 / 102,662,416 / 102,673,529 / 2.50E-05
11 / 1 / C1orf14 / 181,135,622 / 181,189,176 / 2.70E-05
12 / 1 / ARHGEF19 / 16,397,185 / 16,411,691 / 3.30E-05
13 / 8 / CYP7A1 / 59,565,290 / 59,575,274 / 4.70E-05
14 / 22 / DDT / 22,643,553 / 22,652,019 / 9.30E-05
Note: the critical p-value is 0.05/17520 = 2.85 x 10-6. (No genes met this criterion for either ALT or AST)
Page 1 of 19
Supplementary Table 3. Associations for other phenotypes at the SNPs which show significant associations for GGT. The Bonnferroni-corrected p for 80 comparisons (8 phenotypes, 5 SNPs 2 cohorts) is 0.00063, and rs1169288 meets this criterion (with opposite effect directions) for C-reactive protein and for LDL-C. H2 is the proportion of phenotypic variance (in ALT, AST, BMI etc.) associated with the SNP.
Adolescents / AdultsSNP / Allele / Beta / SE / H2 / P / Beta / SE / H2 / P
rs1169288 / ALT (log) / A / 0.018 / 0.033 / 0.01% / 0.97 / 0.004 / 0.017 / 0.00% / 0.83
AST (log) / A / -0.001 / 0.033 / 0.00% / 0.59 / -0.020 / 0.017 / 0.02% / 0.23
BMI / A / 0.059 / 0.033 / 0.15% / 0.073 / 0.013 / 0.019 / 0.01% / 0.48
CRP (log) / A / 0.055 / 0.060 / 0.13% / 0.36 / 0.063 / 0.017 / 0.19% / 0.00024
Glucose / A / 0 / 0.037 / 0.00% / 0.99 / -0.023 / 0.018 / 0.03% / 0.21
HDL-C / A / 0.069 / 0.034 / 0.20% / 0.046 / -0.018 / 0.017 / 0.01% / 0.29
LDL-C / A / -0.044 / 0.034 / 0.08% / 0.21 / -0.078 / 0.017 / 0.26% / 3.90E-06
Triglycerides (log) / A / -0.085 / 0.034 / 0.32% / 0.0122 / -0.009 / 0.017 / 0.00% / 0.6
rs1497406 / ALT (log) / G / 0.049 / 0.031 / 0.12% / 0.97 / 0.046 / 0.016 / 0.10% / 0.0049
AST (log) / G / -0.001 / 0.032 / 0.00% / 0.118 / 0.022 / 0.016 / 0.02% / 0.17
BMI / G / 0.001 / 0.031 / 0.00% / 0.98 / 0.010 / 0.018 / 0.01% / 0.56
CRP (log) / G / -0.002 / 0.058 / 0.00% / 0.107 / 0.010 / 0.016 / 0.01% / 0.54
Glucose / G / -0.018 / 0.035 / 0.02% / 0.6 / -0.005 / 0.017 / 0.00% / 0.76
HDL-C / G / 0.001 / 0.033 / 0.00% / 0.97 / -0.033 / 0.016 / 0.05% / 0.035
LDL-C / G / 0.022 / 0.033 / 0.02% / 0.51 / 0.022 / 0.016 / 0.02% / 0.16
Triglycerides (log) / G / 0.024 / 0.033 / 0.03% / 0.46 / 0.034 / 0.016 / 0.06% / 0.03
rs340005 / ALT (log) / A / 0.104 / 0.032 / 0.51% / 0.017 / 0.028 / 0.017 / 0.04% / 0.096
AST (log) / A / 0.077 / 0.032 / 0.27% / 0.00103 / 0.016 / 0.016 / 0.01% / 0.32
BMI / A / -0.032 / 0.032 / 0.05% / 0.31 / 0.034 / 0.018 / 0.05% / 0.053
CRP (log) / A / -0.005 / 0.057 / 0.00% / 0.94 / 0 / 0.016 / 0.00% / 0.99
Glucose / A / -0.002 / 0.036 / 0.00% / 0.96 / -0.030 / 0.017 / 0.06% / 0.08
HDL-C / A / -0.016 / 0.034 / 0.01% / 0.64 / 0.029 / 0.016 / 0.04% / 0.068
LDL-C / A / -0.026 / 0.034 / 0.03% / 0.44 / 0.006 / 0.016 / 0.00% / 0.73
Triglycerides (log) / A / 0.031 / 0.033 / 0.05% / 0.35 / -0.011 / 0.016 / 0.01% / 0.5
rs5751901 / ALT (log) / T / -0.001 / 0.033 / 0.00% / 0.24 / 0.007 / 0.017 / 0.00% / 0.67
AST (log) / T / 0.039 / 0.033 / 0.07% / 0.97 / 0.022 / 0.017 / 0.02% / 0.18
BMI / T / 0.014 / 0.033 / 0.01% / 0.68 / -0.011 / 0.019 / 0.01% / 0.56
CRP (log) / T / 0.018 / 0.062 / 0.01% / 0.77 / 0.002 / 0.017 / 0.00% / 0.9
Glucose / T / 0.025 / 0.037 / 0.02% / 0.56 / -0.008 / 0.018 / 0.00% / 0.66
HDL-C / T / 0 / 0.035 / 0.00% / 1 / 0.010 / 0.017 / 0.00% / 0.54
LDL-C / T / -0.041 / 0.035 / 0.07% / 0.24 / -0.030 / 0.017 / 0.04% / 0.073
Triglycerides (log) / T / -0.018 / 0.035 / 0.01% / 0.6 / 0.016 / 0.017 / 0.01% / 0.34
rs944002 / ALT (log) / A / -0.004 / 0.038 / 0.00% / 0.73 / -0.028 / 0.02 / 0.03% / 0.16
AST (log) / A / 0.013 / 0.038 / 0.01% / 0.91 / -0.015 / 0.019 / 0.01% / 0.44
BMI / A / 0.040 / 0.039 / 0.05% / 0.3 / 0.013 / 0.022 / 0.01% / 0.54
CRP (log) / A / -0.005 / 0.072 / 0.00% / 0.95 / 0.006 / 0.02 / 0.00% / 0.75
Glucose / A / -0.038 / 0.043 / 0.05% / 0.38 / 0.016 / 0.021 / 0.01% / 0.44
HDL-C / A / 0.059 / 0.041 / 0.11% / 0.15 / -0.028 / 0.019 / 0.03% / 0.146
LDL-C / A / 0.023 / 0.041 / 0.02% / 0.57 / -0.012 / 0.02 / 0.00% / 0.55
Triglycerides (log) / A / 0.035 / 0.041 / 0.04% / 0.39 / -0.007 / 0.019 / 0.00% / 0.73
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Supplementary Table 4. Comparison of mean serum GGT results between adults and adolescents, by genotype at rs6519519 in GGT1.
Adult Studies / Adolescent StudiesLog(GGT)
Mean, (N) / Geometric
mean / Log(GGT)
Mean, (N) / Geometric
mean
QIMR / 1.329 (8041) / 21.3 / 1.086 (2546) / 12.2
NTR / 1.426 (2130) / 26.7 / - / -
Raine, Age 13-15 / - / - / 1.035 (1149) / 10.8
Raine, Age 16-18 / - / - / 1.124 (1046) / 13.3
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Supplementary Table 5. List of genes containing SNPs showing associations with GGT at P < 0.001 and also with coronary artery disease, inflammatory disorders, and Type 2 diabetes, as identified by Ingenuity Pathway Analysis®.
Function Annotation / N of Molecules(out of 321) / p / Molecules
affects non-insulin-dependent diabetes mellitus / 97 / 9.14E-24 / A2BP1, ABCA4, ACSS1, ALK, ANK3, ARHGAP42, ASTN2 (includes EG:23245), AUTS2 (includes EG:26053), BBS9, C14ORF143, CA12, CACNA2D3, CADPS, CALN1, CAPN13, CDC42, CETP, CNBD1, CNTN4, CNTN5, CNTNAP2, CNTNAP5 (includes EG:129684), CSGALNACT1, CTNNA3, DAB1, DCC, DSCAM, DSCAML1, EEF2K, ELMO1, ESR1, FAM114A1, FARS2, FCHO1, FHIT, FOXN3, FRAS1, FRMD6, FTO, GPR144, GRIP1, HHAT, HNF1A, HNF1B, HNF4A, HS6ST3 (includes EG:266722), JAG1, KALRN, KCTD16, KDM2B, KIAA1211, KIRREL3, KSR2, LARS2, LINGO2, LRFN2, MAGI2, MCTP1, MCTP2, MDGA2, MKLN1, MSH6, MYO10, MYO18B, NCAM2, NHEDC1, ODZ2, OLA1, OSBPL3, PAPPA2 (includes EG:60676), PARD3B, PCSK5, PDE4D, RGS6, RIMS1, RNF34, ROBO2, RORA, RYR2, SLC8A1, SORCS1, SOX6, SOX5 (includes EG:6660), SPAG16, TMEFF2, TMEM108, TNNI3K, TNR, TRPM3, TSPAN5, TTC13, TTC35, UBE2D3 (includes EG:7323), UHRF1BP1, XYLT1, ZFYVE28, ZNF423
affects Crohn's disease / 84 / 6.95E-22 / A2BP1, ADAMTS2, AFF3, ANK2, ASTN2 (includes EG:23245), AUTS2 (includes EG:26053), BCKDHB, C14ORF143, CA12, CACNA2D3, CAMK1D, CAPN13, CDH4 (includes EG:1002), CNBD1, CNTN5, CNTNAP2, CNTNAP5 (includes EG:129684), CR1, CSGALNACT1, CTNNA3, CTNND2, CUBN, DAB1, DCC, DLG5, DSCAM, ELMO1, ERAP2, ERBB4, ESR1, FAF1, FAM107B, FAM114A1, FHIT, FOXN3, FRAS1, GALNTL4, GRB2, HS6ST3 (includes EG:266722), ICA1, KALRN, KCNH7, KIAA1211, KIRREL3, LINGO2, LRFN2, LRFN5, LUZP2, MAGI2, MAPT, MDGA2, MYLK, MYO18B, NCAM2, NOD2, ODZ2, OSBPL3, OSBPL8, PACRG, PAPPA, PARD3B, PCSK5, PDE4D, REEP3, RGS6, RUNX1, RYR2, SLC8A1, SLCO1B3, SMURF1, SORCS1, SOX6, SOX5 (includes EG:6660), STK39, STX8, SULF2, TMEFF2, TNFRSF19, TPD52, TRPM3, UHRF1BP1, UST, ZFYVE28, ZNF221
affects inflammatory bowel disease / 85 / 1.89E-20 / A2BP1, ADAMTS2, AFF3, ANK2, ASTN2 (includes EG:23245), AUTS2 (includes EG:26053), BCKDHB, C14ORF143, CA12, CACNA2D3, CAMK1D, CAPN13, CD40, CDH4 (includes EG:1002), CNBD1, CNTN5, CNTNAP2, CNTNAP5 (includes EG:129684), CR1, CSGALNACT1, CTNNA3, CTNND2, CUBN, DAB1, DCC, DLG5, DSCAM, ELMO1, ERAP2, ERBB4, ESR1, FAF1, FAM107B, FAM114A1, FHIT, FOXN3, FRAS1, GALNTL4, GRB2, HS6ST3 (includes EG:266722), ICA1, KALRN, KCNH7, KIAA1211, KIRREL3, LINGO2, LRFN2, LRFN5, LUZP2, MAGI2, MAPT, MDGA2, MYLK, MYO18B, NCAM2, NOD2, ODZ2, OSBPL3, OSBPL8, PACRG, PAPPA, PARD3B, PCSK5, PDE4D, REEP3, RGS6, RUNX1, RYR2, SLC8A1, SLCO1B3, SMURF1, SORCS1, SOX6, SOX5 (includes EG:6660), STK39, STX8, SULF2, TMEFF2, TNFRSF19, TPD52, TRPM3, UHRF1BP1, UST, ZFYVE28, ZNF221
affects coronary artery disease / 82 / 9.59E-19 / A2BP1, ABL1, ADAMTS2, AFF3, ALK, ANK3, ARHGAP42, ASTN2 (includes EG:23245), AUTS2 (includes EG:26053), C14ORF143, CACNA2D3, CADPS, CALN1, CAPN5, CDC42, CDH4 (includes EG:1002), CNTN4, CNTN5, CNTNAP2, CNTNAP5 (includes EG:129684), CORO2A, CTNNA3, CTNND2, DAB1, DCC, DCP1A, DLG5, DSCAM, DSCAML1, EGFR, ELMO1, ERAP2, ETS2, FAF1, FAM107B, FAM114A1, FCHO1, FHIT, FOXN3, FRAS1, HHAT, HMGCLL1, HS6ST3 (includes EG:266722), KALRN, KCNMA1, KCTD16, KLHL29, LAMA4, LINGO2, LOXHD1, LRPAP1, LUZP2, MAGI2, MCTP1, MDGA2, MED15, MYLK, MYO10, MYO18B, ODZ2, OSBPL3, OSBPL8, PARD3B, PCSK5, PDE4D, PLXNA2, PTPRD, RIMS1, RORA, SEMA5A, SOX6, SOX5 (includes EG:6660), SPAG16, STK39, STX8, TNIK, TRPM1, TRPM3, TTC13, UHRF1BP1, XYLT1, ZFYVE28
affects hypertension / 76 / 1.13E-18 / A2BP1, ABCA4, ABL1, ACSL5, AFF3, ALK, ANK2, ANXA2, ARHGEF3, ASTN2 (includes EG:23245), ATG10, AUTS2 (includes EG:26053), C14ORF143, CA12, CACNA2D3, CADPS, CDC42, CNBD1, CNTN4, CNTN5, CNTNAP2, CNTNAP5 (includes EG:129684), CSGALNACT1, CTNNA3, CTNND2, DAB1, DCC, DSCAM, ELMO1, ENPEP, EPAS1, ERBB4, ESR1, FAM107B, FAM108C1, FCHO1, FGD5, FHIT, HHAT, HS6ST3 (includes EG:266722), ICA1, JAG1, KCNH7, KCNMA1, KIF26B, KIRREL3, KSR2, LUZP2, MAGI2, MCTP1, MDGA2, MGAT5B, MYBPC1, MYO18B, NHEDC1, OSBPL3, PAPPA2 (includes EG:60676), PCSK5, PDE4D, RFX3, RGS6, RORA, RYR2, SLC8A1, SOX6, SOX5 (includes EG:6660), SPAG16, STK39, TNIK, TRPM3, UBE2D3 (includes EG:7323), UHRF1BP1, VCAN, XYLT1, ZDHHC6, ZFPM2
affects progressive motor neuropathy / 80 / 5.13E-18 / A2BP1, ALK, ANXA2, ARHGEF37, ASTN2 (includes EG:23245), BAD, BBS9, CA12, CACNA2D3, CALN1, CAMK1D, CAPN13, CD9, CD40, CDH4 (includes EG:1002), CENPC1, CLDN10, CNTN4, CNTN5, CNTNAP5 (includes EG:129684), COL7A1, CTNNA3, CTNND2, DAB1, DCC, DSCAM, DSCAML1, ERBB4, ESR1, ETS2, FARS2, FGD5, FHIT, FSTL5, FTO, GRIP1, HNF1B, HS6ST3 (includes EG:266722), HUS1, ILDR1, KCNMA1, KLHL29, KSR2, LINGO2, LOXHD1, LUZP2, MAGI2, MAPT, MBP, MKLN1, MYO10, MYO18B, NSMAF, ODZ2, PACRG, PARD3B, PDE4D, PLXNA2, PPP1R16B, PTPRD, RAMP3, RGS6, RORA, RUNX1, SEMA5A, SEPT9, SGSM1, SLC17A6, SLC8A3, SOX5 (includes EG:6660), SPAG16, STAP1, TAP2, TNIK, TPT1 (includes EG:7178), TRPM1, UST, VCAN, ZFPM2, ZNF423
affects amyotrophic lateral sclerosis / 52 / 1.31E-16 / A2BP1, ALK, ARHGEF37, BAD, BBS9, CACNA2D3, CALN1, CAMK1D, CAPN13, CDH4 (includes EG:1002), CNTN4, COL7A1, CTNNA3, CTNND2, DAB1, DCC, DSCAM, ERBB4, ESR1, ETS2, FARS2, FHIT, FTO, GRIP1, HNF1B, KCNMA1, KLHL29, KSR2, LOXHD1, LUZP2, MAGI2, MKLN1, MYO10, MYO18B, NSMAF, ODZ2, PACRG, PLXNA2, PPP1R16B, PTPRD, RAMP3, RGS6, RORA, SEPT9, SGSM1, SPAG16, STAP1, TNIK, TRPM1, VCAN, ZFPM2, ZNF423
affects insulin-dependent diabetes mellitus) / 66 / 9.01E-13 / A2BP1, AFF3, ALK, ANK2, ANK3, ASTN2 (includes EG:23245), ATF2, CACNA2D3, CADPS, CAPN13, CCNB1IP1, CDC16, CNTN4, CNTN5, CTNNA3, CUBN, DAB1, DCC, DENND1A, DERA, DGKI, DSCAM, DSCAML1, ELMO1, EPAS1, ERBB4, FHIT, FRAS1, FTO, GALNTL4, HNF1A, HS6ST3 (includes EG:266722), JAG1, KANK4, KCNH7, KCTD16, KIF26B, KIRREL3, KLHL29, KSR2, LINGO2, LUZP2, MAGI2, ME3, MED15, MYLK, NOD2, OR4D6, PAPPA, PARD3B, PITPNC1, PKD1L1, PRUNE2, RGS6, RUNX1, RYR2, SEMA5A, SOX6, SOX5 (includes EG:6660), TAP2, TRIM26, TRPM3, UHRF1BP1, VCAN, XYLT1, ZNF366
affects rheumatoid arthritis / 80 / 8.75E-11 / A2BP1, ADAMTS2, AFF3, AGBL3, ASTN2 (includes EG:23245), AUTS2 (includes EG:26053), BCKDHB, C6ORF142, CADPS, CAMK1D, CAPN13, CCNB1IP1, CD40, CDC16, CHST9, CNTN4, CNTN5, CNTNAP2, CORO2A, CR1, CSGALNACT1, CTNNA3, CUBN, DAB1, DACH1, DCC, DENND1A, DGKI, DSCAM, DSCAML1, ELAVL4, ELMO1, EPAS1, FAF1, FARS2, FHIT, FSTL5, FTO, HMGCLL1, HS6ST3 (includes EG:266722), IL16, KCNH5, KCNH7, KCNMA1, KIRREL3, KSR2, LARS2, LINGO2, LRFN2, MAGI2, MCC, MICAL3 (includes EG:57553), MYO10, MYO18B, NOD2, ODZ2, PAPPA, PARD3B, PDE4D, PKD1L1, PRUNE2, RFX3, RGS6, RIMS1, RUNX1, RYR2, SERINC3, SOX6, SOX5 (includes EG:6660), SPAG16, SPPL3, TAP2, TNIK, TNNI3K, TRIM26, TRRAP, UHRF1BP1, WDR70, XYLT1, ZNF366
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Supplementary Table 6. Characteristics of study participants in the Australian studies (means and standard deviations, and geometric means for the log-transformed variables).
Adults / AdolescentsMales / Females / Males / Females
N / 3725 / 6246 / 1235 / 1320
Age (years) / 46.9 ± 12.4 / 45.5 ± 12.8 / 14.7 ± 1.9 / 15.0 ± 2.3
BMI (kg/m2) / 26.7 ± 4.1 / 25.5 ± 5.0 / 20.6 ± 3.6 / 20.8 ± 3.6
Log10 GGT (u/l) / 1.46 ± 0.29
(28.8) / 1.23 ± 0.26
(17.0) / 1.13 ± 0.14
(13.5) / 1.05 ± 0.14
(11.2)
Log10 ALT (u/l) / 1.44 ± 0.21
(27.5) / 1.24 ± 0.20
(17.4) / 1.19 ± 0.18
(15.5) / 1.12 ± 0.16
(13.2)
Log10 AST (u/l) / 1.41 ± 0.14
(25.7) / 1.32 ± 0.13
(20.9) / 1.39 ± 0.10
(24.5) / 1.31 ± 0.10
(20.4)
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Supplementary Table 7. Details related to the gene network shown in Figure 3. Genes are ordered by the p-value for the most significant SNP.
Symbol / Entrez Gene Name / SNP / p-value for log(GGT)HNF1A / HNF1 homeobox A / rs2259820 / 2.50E-16
RORA / RAR-related orphan receptor A / rs340005 / 3.80E-08
RNF34 / ring finger protein 34 / rs7296507 / 2.20E-05
HNF4A / hepatocyte nuclear factor 4, alpha / rs6031595 / 9.40E-05
TRRAP / transformation/transcription domain-associated protein / rs6465726 / 1.00E-04
ELMO1 / engulfment and cell motility 1 / rs2814966 / 2.00E-04
FHIT / fragile histidine triad gene / rs780354 / 2.00E-04
OSBPL3 / oxysterol binding protein-like 3 / rs17150460 / 2.00E-04
RSU1 / Ras suppressor protein 1 / rs3808925 / 2.00E-04
SDCBP / syndecan binding protein (syntenin) / rs3808609 / 2.00E-04
SLC22A12 / solute carrier family 22 (organic anion/urate transporter), member 12 / rs10897518 / 2.00E-04
SMURF1 / SMAD specific E3 ubiquitin protein ligase 1 / rs7791007 / 2.00E-04
TNFAIP1 / tumor necrosis factor, alpha-induced protein 1 (endothelial) / rs2234116 / 2.00E-04
TTC35 / tetratricopeptide repeat domain 35 / rs6986900 / 2.00E-04
CDH4 / cadherin 4, type 1, R-cadherin (retinal) / rs11906745 / 3.00E-04
ENPEP / glutamyl aminopeptidase (aminopeptidase A) / rs1879053 / 3.00E-04
ZNF221 / zinc finger protein 221 / rs435957 / 3.00E-04
ANXA2 / annexin A2 / rs11629852 / 4.00E-04
FAM107B / family with sequence similarity 107, member B / rs7922166 / 4.00E-04
MCC / mutated in colorectal cancers / rs2120348 / 4.00E-04
UBE2D3 / ubiquitin-conjugating enzyme E2D 3 (UBC4/5 homolog, yeast) / rs223401 / 4.00E-04
ZDHHC6 / zinc finger, DHHC-type containing 6 / rs2306160 / 4.00E-04
HNF1B / HNF1 homeobox B / rs757210 / 5.00E-04
LHX6 / LIM homeobox 6 / rs12237553 / 5.00E-04
MED15 / mediator complex subunit 15 / rs11090206 / 5.00E-04
MLXIPL / MLX interacting protein-like / rs1051921 / 5.00E-04
MSH6 / mutS homolog 6 (E. coli) / rs7562048 / 5.00E-04
PARD3B / par-3 partitioning defective 3 homolog B (C. elegans) / rs849248 / 5.00E-04
ZNF214 / zinc finger protein 214 / rs10839691 / 6.00E-04
LARS2 / leucyl-tRNA synthetase 2, mitochondrial / rs965238 / 7.00E-04
MTRF1L / mitochondrial translational release factor 1-like / rs4936281 / 7.00E-04
SLC25A19 / solute carrier family 25 (mitochondrial thiamine pyrophosphate carrier), member 19 / rs4788883 / 7.00E-04
TRAF4 / TNF receptor-associated factor 4 / rs2070265 / 7.00E-04
TRAF3IP1 / TNF receptor-associated factor 3 interacting protein 1 / rs7598777 / 7.00E-04
CHST9 / carbohydrate (N-acetylgalactosamine 4-0) sulfotransferase 9 / rs16943045 / 8.00E-04
ACN9 / ACN9 homolog (S. cerevisiae) / rs1199292 / 9.00E-04
ADAMTS2 / ADAM metallopeptidase with thrombospondin type 1 motif, 2 / rs6862563 / 9.00E-04
FCHO1 / FCH domain only 1 / rs12979056 / 9.00E-04
NOD2 / nucleotide-binding oligomerization domain containing 2 / rs1077861 / 9.00E-04
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Supplementary Figure 1. Allelic associations at significant loci for GGT, combined adult and adolescent data (A to D for chromosomes 1, 12, 14 and 15). Blue lines show recombination rates and red shading indicates the strength of linkage disequilibrium with the most significant SNP in each age-group.
A.
B.
C.
D.
Supplementary Figure 2. Chromosome 7 allelic associations with (A) GGT, (B) ALT, and (C) AST, in combined adult and adolescent data. Blue lines show recombination rates and red shading indicates the strength of linkage disequilibrium with the most significant SNP in each age-group.
A)
B)
C)
Supplementary Figure 3. Chromosome 22, GGT1 locus, allelic associations in (A) adults, (B) adolescents and (C) heterogeneity between adult and adolescent associations. Blue lines show recombination rates and red shading indicates the strength of linkage disequilibrium with the most significant SNP in each age-group.
A)Adults
B)Adolescents
C)Heterogeneity
Supplementary Figure 4. Q-Q plots for (A) association in the combined adult and adolescent data and (B) heterogeneity between adult and adolescent SNP associations.
(A)
(B)
[Note thatp = 5 x 10-8 is approximately 33 on the -2Ln(p) scale]
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