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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.