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Table 1 Result of the 10 most nominally significant interactions

From: The genetic interacting landscape of 63 candidate genes in Major Depressive Disorder: an explorative study

A: Additive dominant
Marker 1 Marker 2 Interaction statistics
            Cases/Controls with marker 1 and marker 2 conferring risk (1) or no-risk (0)
         Permuted    
Chr Gene Rs Chr Gene Rs AP (95% C.I.) AP P P PAF AUC 00 01 10 11
4 ARHGAP10 rs9332471 4 ARHGAP10 rs6845865 0.58 (0.39:0.78) 9.10E-9 0.14 0.147 0.5153 1009/1073 169/174 475/500 78/33
6 HTR1E rs6922679 16 GRIN2A rs17570500 *0.71 (0.42:1.002) 1.92E-6 0.57 0.142 0.5046 48/50 20/6 1332/1388 310/321
4 ARHGAP10 rs9332471 4 ARHGAP10 rs2306910 0.63 (0.37:0.89) 2.40E-6 0.61 0.149 0.5136 1201/1273 190/182 233/238 35/12
4 ARHGAP10 rs9991394 4 ARHGAP10 rs12645249 0.59 (0.34:0.84) 2.58E-6 0.63 0.146 0.5173 1162/1257 332/326 154/158 47/18
9 GRIN3A rs7873495 11 GRIK4 rs10892635 **-1.08 (-1.56:-0.59) 1.26E-5 0.90 0.139 0.5216 290/258 10/30 1308/1390 122/105
12 GRIN2B rs12371702 9 GRIN3A rs13292935 ***-0.92 (-1.35:-0.50) 1.89E-5 0.95 0.146 0.5375 1003/1122 442/377 236/202 51/82
12 GRIN2B rs11832404 4 NR3C2 rs982076 **-1.23 (-1.81:-0.65) 3.49E-5 0.99 0.142 0.5266 257/182 10/24 1268/1367 92/86
12 GRIN2B rs11832404 11 GRIK4 rs7928347 **-1.27 (-1.89:-0.66) 5.24E-5 0.99 0.142 0.5300 255/185 7/18 1234/1332 87/78
4 ARHGAP10 rs9332471 9 SLC1A1 rs184204 0.53 (0.27:0.79) 6.28E-5 0.99 0.145 0.5157 1212/1292 194/183 271/282 53/23
5 GRIA1 rs17114975 12 GRIN2B rs1012587 *0.64 (0.33:0.95) 6.54E-5 0.99 0.129 0.5084 83/79 24/8 1381/1448 241/245
B: Additive recessive
Marker 1 Marker 2 Interaction statistics
            Cases/Controls with marker 1 and marker 2 conferring risk (1) or no-risk (0)
         Permuted    
Chr Gene Rs Chr Gene Rs AP (95% C.I.) AP P P PAF AUC 00 01 10 11
9 RNF20 rs16920473 12 GRIN2B rs2216127 0.69 (0.42:0.97) 7.65E-7 0.56 0.149 0.5238 377/446 1296/1305 12/14 46/14
4 ARHGAP10 rs4835456 11 GRIK4 rs4936540 0.72 (0.42:1.02) 2.70E-6 0.72 0.148 0.5136 1105/1176 22/23 582/571 22/6
4 ARHGAP10 rs6824449 16 SLC6A2 rs192303 ***-1.28 (-1.85:-0.72) 8.30E-6 0.86 0.149 0.5319 1293/1414 208/159 184/144 16/32
16 GRIN2A rs4782040 11 GRIK4 rs11218032 ***-0.99 (-1.43:-0.55) 8.73E-6 0.87 0.149 0.5211 1244/1306 122/126 250/207 9/32
12 GRIN2B rs3764030 5 HTR4 rs6865654 0.68 (0.37:0.99) 1.27E-5 0.91 0.148 0.5063 1363/1423 47/48 231/235 22/7
11 GRIK4 rs7939968 4 NR3C2 rs12641471 0.52 (0.28:0.76) 2.03E-5 0.94 0.144 0.5170 1088/1165 192/186 275/292 69/32
4 ARHGAP10 rs6824449 16 GRIN2A rs11640235 ***-1.01 (-1.56:-0.55) 3.60E-5 0.98 0.149 0.5204 1355/1435 210/163 105/108 8/25
11 GRIK4 rs7939968 4 NR3C2 rs4835508 0.51 (0.27:0.75) 3.77E-5 0.98 0.143 0.5186 1029/1118 185/179 275/295 70/33
11 GRIK4 rs7939968 4 ARHGAP10 rs12641157 0.64 (0.33:0.94) 5.05E-5 0.99 0.148 0.5178 1347/1444 260/229 93/95 26/8
3 HTR3C rs6766410 6 LAMA4 rs6913656 ***-0.84 (-1.25:-0.43) 5.48E-5 0.99 0.148 0.5216 1210/1279 243/207 217/218 21/49
C: Multiplicative dominant
Marker 1 Marker 2 Interaction statistics
            Cases/Controls with marker 1 and marker 2 conferring risk (1) or no-risk (0)
         Permuted    
Chr Gene Rs Chr Gene Rs OR (95% C.I.) P P PAF AUC 00 01 10 11
4 GRIA2 rs17244157 16 GRIN2A rs1861192 0.44 (0.30:0.64) 2.39E-5 0.85 0.120 0.5442 712/838 175/120 589/539 98/120
9 SLC1A1 rs10974611 6 LAMA4 rs2032568 0.47 (0.38:0.67) 3.60E-5 0.92 0.125 0.5389 536/624 154/116 699/682 145/195
12 GRIN2B rs12371702 9 GRIN3A rs13292935 0.41 (0.26:0.62) 3.72E-5 0.95 0.114 0.5375 1003/1122 442/377 236/202 51/82
4 GRIA2 rs17244157 16 GRIN2A rs16966731 0.45 (0.31:0.66) 3.78E-5 0.95 0.127 0.5322 572/642 147/88 798/808 135/162
21 GRIK1 rs379182 11 GRIK4 rs17124632 0.24 (0.12:0.48) 4.41E-5 0.97 0.148 0.5244 80/111 46/14 1165/1221 357/342
10 RPP30 rs11186343 7 HTR5A rs2919435 2.49 (1.60:3.89) 5.51E-5 0.98 0.130 0.5295 145/97 58/89 951/1028 558/555
3 NR1I2 rs6438549 12 GRIN2B rs12823982 0.45 (0.30:0.67) 7.17E-5 0.99 0.114 0.5333 927/1011 222/182 505/473 67/105
13 HTR2A rs666693 22 COMT rs8185002 3.05 (1.75:5.31) 8.82E-5 0.99 0.148 0.5325 596/548 34/61 927/1011 83/58
4 NR3C2 rs7691663 5 GRIA1 rs1422897 2.09 (1.44:3.02) 1.02E-4 0.99 0.110 0.5310 124/85 445/490 185/237 977/964
19 GRIK5 rs4803523 5 GRIA1 rs13359392 2.31 (1.51:3.55) 1.27E-4 1.0 0.144 0.5350 548/487 58/90 962/1068 161/135
D: Multiplicative recessive
Marker 1 Marker 2 Interaction statistics
            Cases/Controls with marker 1 and marker 2 conferring risk (1) or no-risk (0)
         Permuted    
Chr Gene Rs Chr Gene Rs OR (95% C.I.) P P PAF AUC 00 01 10 11
5 GRIA1 rs574071 11 HTR3B rs1672717 0.52 (0.39:0.71) 2.72E-5 0.70 0.132 0.5433 371/473 701/646 222/182 305/346
4 NR3C2 rs7691663 5 GRIA1 rs9686702 1.84 (1.38:2.44) 3.28E-5 0.76 0.117 0.5375 270/211 313/374 445/516 703/679
3 GSK3B rs1719889 16 GRIN2A rs1102967 0.55 (0.41:0.73) 3.30E-5 0.76 0.139 0.5423 228/345 569/517 308/289 534/552
11 GRIA4 rs17104807 22 COMT rs2020917 2.39 (1.57:3.63) 4.56E-5 0.86 0.118 0.5386 98/86 643/719 86/149 848/784
12 GRIN2B rs3764030 16 GRIN2A rs1868289 4.99 (2.26:11.03) 6.95E-5 0.96 0.133 0.5169 41/13 29/44 695/742 948/970
5 GRIA1 rs574071 16 GRIN2A rs1070548 2.21 (1.48:3.31) 1.17E-4 0.99 0.142 0.5284 517/532 819/860 70/110 186/135
9 NTRK2 rs1624327 16 GRIN2A rs1097784 1.94 (1.38:2.72) 1.19E-4 0.99 0.138 0.5332 562/581 639/662 128/186 237/178
4 ARHGAP10 rs6824449 16 SLC6A2 rs192303 0.27 (0.14:0.54) 1.68E-4 1.0 0.119 0.5319 1293/1414 208/159 184/144 16/32
6 GRIK2 rs7770500 6 LAMA4 rs2072019 2.06 (1.41:3.00) 1.76E-4 1.0 0.116 0.5133 139/102 666/719 119/164 792/781
9 SLC1A1 rs7022369 5 GRIA1 rs12658202 1.92 (1.36:2.71) 1.98E-4 1.0 0.067 0.5285 100/147 281/326 399/352 957/952
E: MDR
Marker 1 Marker 2 Interaction statistics
           Cases/Controls with genotype combination at predicted risk group
Chr Gene Rs Chr Gene Rs Balanced accuracy PAF OR (95% C.I.) P High risk Low risk TPR FPR
12 GRIN2B rs1012587 3 HTR3C rs6762938 0.5513 0.0980 1.51 (1.32:1.73) 1.168E-09 907/751 825/1032 0.524 0.421
16 GRIN2A rs8045893 3 HTR3C rs6762938 0.5498 0.0900 1.49 (1.30:1.71) 4.452E-09 1033/887 699/896 0.596 0.497
6 HTR1E rs17222848 5 GRIA1 rs17515709 0.5480 0.0950 1.47 (1.28:1.68) 1.707E-08 933/790 799/993 0.539 0.443
11 GRIA4 rs609665 6 GRIK2 rs2518171 0.5476 0.0917 1.46 (1.28:1.68) 2.051E-08 982/842 750/941 0.567 0.472
6 GRIK2 rs17828670 3 GSK3B rs6771023 0.5470 0.0894 1.46 (1.28:1.67) 2.757E-08 1021/884 711/899 0.589 0.554
13 HTR2A rs9526240 11 BDNF rs6265 0.5468 0.0912 1.45 (1.27:1.66) 3.643E-08 984/847 748/936 0.568 0.475
16 SLC6A2 rs1814270 6 FKBP5 rs9462104 0.5465 0.1020 1.46 (1.28:1.68) 3.031E-08 809/668 923/1115 0.467 0.375
13 HTR2A rs17288723 9 GRIN3A rs11788456 0.5454 0.0937 1.44 (1.26:1.64) 8.039E-08 936/802 796/981 0.540 0.500
12 GRIN2B rs10845847 12 GRIN2B rs12301788 0.5454 0.0809 1.48 (1.29:1.71) 2.458E-08 1180/1053 552/730 0.681 0.591
17 SLC6A4 rs2020939 6 GRIK2 rs2749074 0.5448 0.1012 1.44 (1.26:1.65) 8.982E-08 812/677 920/1106 0.469 0.380
  1. Linear models are presented in A-D and results from MDR analysis in E. All top interactions of each method are LD filtered (r2 < 0.2).
  2. Abbreviations:
  3. AP, attributable proportion due to interaction; Permuted P, permuted P value corrected for multiple comparisons; 00, 01, 10 and 11 denotes risk (1) or no risk (0) genotype for marker 1 and marker 2; OR, odds ratio estimates for the interaction term in the multiplicative method; P values of the multiplicative method are derived for the interaction term; AUC, area under the curve metrics derived from the ROC analysis (metrics of diagnose classifier for a particular set of par-wise markers); For the MDR method OR’s are calculated using the number of cases/controls in high and low risk groups as defined in the MDR analysis; Balanced accuracy, statistical metrics estimate how accurate individuals are classified into high versus low risk groups; The MDR P values are derived from test for significance of the OR estimates; TPR (true positive rate) and FPR (false positive rate) is the sensitivity and specificity metrics to test the diagnose classifier for a particular set of pair-wise markers; PAF, population attributable fraction, proportion of disease burden in the population due to exposure to genetic risk.
  4. Notes: Asterisk (*) denotes that recoding of the preventive factors was made before measures of interaction in the additive scale were calculated. Recoding was done as follows:
  5. *00 to 10, 01 to 11, 10 to 00 & 11 to 01.
  6. **00 to 01, 01 to 11, 10 to 00 & 11 to 10.
  7. ***00 to 11, 01 to 10, 10 to 01 & 11 to 00.
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