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Table 2 Integrated analyses for drug response for either (A) Gemcitabine or (B) AraC

From: Discovery of genetic biomarkers contributing to variation in drug response of cytidine analogues using human lymphoblastoid cell lines

SNP

Probe set

GWAS

rslD

Closest gene

MAF

Chr

Position

Region

Probeset

Gene symbol

Chr

R value (SNP vs IC50)

P value (SNP vs IC50)

R value (SNP vs Exp)

P value (SNP vs Exp)

R value (EXP vs IC50)

P value (EXP vs IC50)

(A) Gemcitabine

rs316871

PLD5

0.097

1

240409507

Intron

225532_at

CABLES1

18

-0.326

4.14E–05

-0.242

6.54E–05

0.347

3.12E–06

rs316823

PLD5

0.093

1

240422651

Intron

225532_at

CABLES1

18

-0.288

2.88E–04

-0.257

2.05E–05

0.347

3.12E–06

rs402098

PLD5

0.093

1

240430321

Intron

225532_at

CABLES1

18

-0.288

2.88E–04

-0.257

2.05E–05

0.347

3.12E–06

rs427498

PLD5

0.087

1

240424078

Intron

225532_at

CABLES1

18

-0.280

4.43E–04

-0.256

2.28E–05

0.347

3.12E–06

rs316823

PLD5

0.093

1

240422651

Intron

225531_at

CABLES1

18

-0.288

2.88E–04

-0.239

7.69E–05

0.321

1.72E–05

rs402098

PLD5

0.093

1

240430321

Intron

225531_at

CABLES1

18

-0.288

2.88E–04

-0.239

7.69E–05

0.321

1.72E-05

rs4392391

C3orf23

0.419

3

44247970

Downstream

1555906_s_at

C3orf23

3

-0.318

5.78E–05

-0.250

3.46E–05

0.263

4.86E–04

rs1565214

C3orf23

0.425

3

44309303

Upstream

1555906_s_at

C3orf23

3

-0.308

1.35E–04

-0.251

4.09E–05

0.263

4.86E–04

rs9809107

C3orf23

0.419

3

44257938

Flanking_5UTR

1555906_s_at

C3orf23

3

-0.301

1.46E–04

-0.242

5.97E–05

0.263

4.86E–04

rs967285

C3orf23

0.422

3

44250280

Downstream

1555906_s_at

C3orf23

3

-0.301

1.48E–04

-0.247

4.36E–05

0.263

4.86E–04

rs9821268

C3orf23

0.413

3

44278128

Upstream

1555906_s_at

C3orf23

3

-0.292

2.43E–04

-0.241

6.29E–05

0.263

4.86E–04

rs1565215

C3orf23

0.418

3

44309103

Upstream

1555906_s_at

C3orf23

3

-0.291

2.64E–04

-0.246

4.62E–05

0.263

4.86E–04

rs10510741

C3orf23

0.445

3

44239198

Flanking_5UTR

1555906_s_at

C3orf23

3

-0.283

3.68E–04

-0.275

4.71E–06

0.263

4.86E–04

rs9852733

C3orf23

0.451

3

44252343

Flanking_5UTR

1555906_s_at

C3orf23

3

-0.279

4.59E–04

-0.268

8.53E–06

0.263

4.86E–04

rs6808448

C3orf23

0.451

3

44218611

Flanking_5UTR

1555906_s_at

C3orf23

3

-0.273

6.19E–04

-0.273

5.38E–06

0.263

4.86E–04

rs9846155

C3orf23

0.456

3

44257844

Flanking_5UTR

1555906_s_at

C3orf23

3

-0.272

6.33E–04

-0.262

1.38E–05

0.263

4.86E–04

rs9284879

C3orf23

0.433

3

44259588

Flanking_5UTR

1555906_s_at

C3orf23

3

-0.264

9.43E–04

-0.253

2.65E–05

0.263

4.86E–04

rs12486452

C3orf23

0.433

3

44299569

Flanking_5UTR

1555906_s_at

C3orf23

3

-0.264

9.43E–04

-0.241

6.45E–05

0.263

4.86E–04

rs12631341

C3orf23

0.433

3

44284272

Flanking_5UTR

1555906_s_at

C3orf23

3

-0.264

9.43E–04

-0.241

6.45E–05

0.263

4.86E–04

rs7631790

C3orf23

0.433

3

44274209

Flanking_5UTR

1555906_s_at

C3orf23

3

-0.264

9.43E–04

-0.241

6.45E–05

0.263

4.86E–04

rs4392391

C3orf23

0.419

3

44247970

Downstream

227978_s_at

ZADH2

18

-0.318

5.78E–05

0.251

3.11E–05

-0.351

2.42E–06

rs1565214

C3orf23

0.425

3

44309303

Upstream

227978_s_at

ZADH2

18

–0.308

1.35E–04

0.246

5.9E–05

-0.351

2.42E–06

rs9809107

C3orf23

0.419

3

44257938

Flanking_5UTR

227978_s_at

ZADH2

18

-0.301

1.46E–04

0.273

5.72E–06

-0.351

2.42E–06

rs967285

C3orf23

0.422

3

44250280

Downstream

227978_s_at

ZADH2

18

-0.301

1.48E–04

0.254

2.58E–05

-0.351

2.42E–06

rs9821268

C3orf23

0.413

3

44278128

Upstream

227978_s_at

ZADH2

18

-0.292

2.43E–04

0.247

4.17E–05

-0.351

2.42E–06

rs1565215

C3orf23

0.418

3

44309103

Upstream

227978_s_at

ZADH2

18

-0.291

2.64E–04

0.250

3.46E–05

-0.351

2.42E–06

rs4682949

C3orf23

0.398

3

44220159

Flanking_5UTR

227978_s_at

ZADH2

18

-0.287

3.01E–04

0.247

4.14E–05

–0.351

2.42E–06

rs10510741

C3orf23

0.445

3

44239198

Flanking_5UTR

227978_s_at

ZADH2

18

-0.283

3.68E–04

0.251

3.03E–05

–0.351

2.42E–06

rs9852733

C3orf23

0.451

3

44252343

Flanking_5UTR

227978_s_at

ZADH2

18

–0.279

4.59E–04

0.239

7.38E–05

–0.351

2.42E–06

rs6808448

C3orf23

0.451

3

44218611

Flanking_5UTR

227978_s_at

ZADH2

18

-0.273

6.19E–04

0.260

1.62E–05

-0.351

2.42E–06

rs9846155

C3orf23

0.456

3

44257844

Flanking_5UTR

227978_s_at

ZADH2

18

-0.272

6.33E–04

0.260

1.58E–05

-0.351

2.42E–06

rs12486452

C3orf23

0.433

3

44299569

Flanking_5UTR

227978_s_at

ZADH2

18

-0.264

9.43E–04

0.239

7.52E–05

-0.351

2.42E–06

rs12631341

C3orf23

0.433

3

44284272

Flanking_5UTR

227978_s_at

ZADH2

18

-0.264

9.43E–04

0.239

7.52E–05

-0.351

2.42E–06

rs7631790

C3orf23

0.433

3

44274209

Flanking_5UTR

227978_s_at

ZADH2

18

-0.264

9.43E–04

0.239

7.52E–05

-0.351

2.42E–06

rs12188464

PIK3RI

0.459

5

67999705

Flanking_5UTR

225935_at

–––

7

-0.309

9.69E–05

0.366

2.47E–06

-0.296

7.99E–05

rs13171512

PIK3RI

0.462

5

68000787

Flanking_5UTR

236170_x_at

–––

7

-0.313

7.86E–05

0.349

7.69E–06

-0.299

6.75E–05

rs13171512

PIK3RI

0.462

5

68000787

Flanking_5UTR

225935_at

–––

7

-0.313

7.86E–05

0.375

1.33E–06

-0.296

7.99E–05

rs7713001

PIK3RI

0.459

5

67999371

Flanking_5UTR

225935_at

–––

7

-0.309

9.69E–05

0.366

2.47E–06

-0.296

7.99E–05

rs12188464

PIK3RI

0459

5

67999705

Flanking_5UTR

201334_s_at

ARHGEF12

11

-0.309

9.69E–05

0.380

9.03E–07

-0.339

5.35E–06

rs13171512

PIK3RI

0.462

5

68000787

Flanking_5UTR

201334_s_at

ARHGEF12

11

-0.313

7.86E–05

0.372

1.59E–06

-0.339

5.35E–06

rs7713001

PIK3RI

0.459

5

67999371

Flanking_5UTR

201334_s_at

ARHGEF12

11

-0.309

9.69E–05

0.380

9.03E–07

-0.339

5.35E–06

rs12188464

PIK3RI

0.459

5

67999705

Flanking_3UTR

238012_at

DPP7

9

-0.309

9.69E–05

0.372

1.63E–06

-0.324

1.45E–05

rs13171512

PIK3RI

0.462

5

68000787

Flanking_3UTR

238012_at

DPP7

9

-0.313

7.86E–05

0.378

1.08E–06

-0.324

1.45E–05

rs7713001

PIK3RI

0.459

5

67999371

Flanking_3UTR

238012_at

DPP7

9

-0.309

9.69E–05

0.372

1.63E–06

-0.324

1.45E–05

rs12188464

PIK3RI

0.459

5

67999705

Flanking_3UTR

225086_at

FAM98B

15

-0.309

9.69E–05

0.345

9.5E–06

-0.352

2.18E–06

rs13171512

PIK3RI

0.462

5

68000787

Flanking_3UTR

225086_at

FAM98B

15

-0.313

7.86E–05

0.354

5.38E–06

-0.352

2.18E–06

rs3135351

HLA–DRA

0.137

6

32500923

Flanking_5UTR

1566082_at

–––

10

0.265

9.48E–04

0.277

4.24E–06

0.320

1.88E–05

rs2472476

NIPSNAP3B

0.389

9

106571777

Intron

200988_s_at

PSME3

17

0.338

1.92E–05

-0.239

7.6E–05

-0.350

.60E–06

rs2928445

IPMK

0.267

10

58816782

Flanking_3UTR

227482_at

ADCK1

14

-0.331

2.76E–05

0.247

4.09E–05

-0.293

9.45E–05

rs12244977

IPMK

0.195

10

58762688

Flanking_3UTR

1569396_at

RAB40C

16

-0.308

1.03E–04

-0.243

5.72E–05

0.303

5.47E–05

rs12256364

IPMK

0.195

10

58765694

Flanking_3UTR

1569396_at

RAB40C

16

-0.308

1.03E–04

-0.243

5.72E–05

0.303

5.47E–05

rs2928445

IPMK

0.267

10

58816782

Flanking_3UTR

226987_at

RBM15B

3

-0.331

2.76E–05

0.263

1.2E–05

-0.354

1.90E–06

rs4774760

PIGB

0.416

15

53376504

upstreaintronm

224856_at

FKBP5

6

0.326

3.63E–05

-0.241

6.7E–05

-0.411

2.15E–08

rs7174876

PIGB

0.416

15

53406853

Upstream

224856_at

FKBP5

6

0.284

4.06E–04

-0.237

9.71E–05

-0.411

2.15E–08

rs2290344

PIGB

0.253

15

53407088

Coding

224856_at

FKBP5

6

0.339

1.75E–05

-0.266

9.87E–06

-0.393

9.66E–08

rs4774760

PIGB

0.416

15

53376504

Upstream

204560_at

FKBP5

6

0.326

3.63E–05

-0.282

2.7E–06

-0.393

9.66E–08

rs12050587

PIGB

0.45

15

53414820

Intron

224856_at

FKBP5

6

0.305

1.23E–04

-0.256

2.27E–05

-0.393

9.66E–08

rs28668016

PIGB

0.365

15

53398725

5UTR

204560_at

FKBP5

6

0.304

1.31E–04

-0.261

1.49E–05

-0.393

9.66E–08

rs11636687

PIGB

0.421

15

53392444

Flanking_5UTR

224856_at

FKBP5

6

0.302

1.53E–04

-0.252

3.34E–05

-0.393

9.66E–08

rs2414409

PIGB

0.448

15

53419009

Intron

204560_at

FKBP5

6

0.299

1.62E–04

-0.264

1.17E–05

-0.393

9.66E–08

rs7183960

PIGB

0.451

15

53409987

Intron

224856_at

FKBP5

6

0.292

2.37E–04

-0.262

1.37E–05

-0.393

9.66E–08

rs7174876

PIGB

0.423

15

53406853

Intron

204560_at

FKBP5

6

0.284

4.06E–04

-0.274

6.06E–06

-0.393

9.66E–08

rs2290344

PIGB

0.253

15

53407088

Coding

224856_at

PIGB

15

0.339

1.75E–05

-0.301

4.81E–07

-0.294

8.98E–05

rs4774760

PIGB

0.416

15

53376504

Upstream

242760_x_at

PIGB

15

0.326

3.63E–05

-0.240

6.85E–05

-0.294

8.98E–05

rs8024695

PIGB

0.285

15

53426597

Intron

242760_x_at

PIGB

15

0.321

5.00E–05

-0.282

2.56E–06

-0.294

8.98E–05

rs28668016

PIGB

0.365

15

53398725

5UTR

242760_x_at

PIGB

15

0.304

1.31E–04

-0.274

5.28E–06

-0.294

8.98E–05

(B) AraC

rs10495285

KIAA0133 (URB2)

0.171

1

227871618

Downstream

219526_at

C14orf169

14

0.393

4.13E–07

-0.240

6.97E–05

-0.318

1.86E–05

rs9861198

Probable leucyl–tRNA synthetase

0.086

3

45310394

Upstream

235936_at

LOC254559

15

0.308

9.07E–05

0.274

5.12E–06

0.294

8.27E–05

rs9816196

U3 small nucleolar RNA

0.055

3

45321382

Upstream

235936_at

LOC254559

15

0.315

6.70E–05

0.242

7.05E–05

0.294

8.27E–05

rs6441911

RIS1

0.055

3

45322523

Flanking_5UTR

235936_at

LOC254559

15

0.315

6.20E–05

0.250

3.26E–05

0.294

8.27E–05

rs9878275

Probable leucyl–tRNA synthetase

0.055

3

45331043

Upstream

235936_at

LOC254559

15

0.311

8.31E–05

0.249

3.79E–05

0.294

8.27E–05

rs9846284

U3 small nucleolar RNA

0.055

3

45331970

Upstream

235936_at

LOC254559

15

0.315

6.20E–05

0.250

3.37E–05

0.294

8.27E–05

rs9850725

LARS2

0.055

3

45332431

Flanking_5UTR

235936_at

LOC254559

15

0.315

6.20E–05

0.250

3.26E–05

0.294

8.27E–05

rs9861198

Probable leucyl–tRNA synthetase

0.086

3

45310394

Upstream

206603_at

SLC2A4

17

0.308

9.07E–05

0.239

7.63E–05

0.345

3.18E–06

rs9816196

U3 small nucleolar RNA

0.055

3

45321382

Upstream

206603_at

SLC2A4

17

0.315

6.70E–05

0.294

1.21E–06

0.345

3.18E–06

rs6441911

RIS1

0.055

3

45322523

Flanking_5UTR

206603_at

SLC2A4

17

0.315

6.20E–05

0.301

4.80E–07

0.345

3.18E–06

rs9878275

Probable leucyl–tRNA synthetase

0.055

3

45331043

Upstream

206603_at

SLC2A4

17

0.311

8.31E–05

0.300

5.67E–07

0.345

3.18E–06

rs9846284

U3 small nucleolar RNA

0.055

3

45331970

Upstream

206603_at

SLC2A4

17

0.315

6.20E–05

0.301

5.03E–07

0.345

3.18E–06

rs9850725

LARS2

0.055

3

45332431

Flanking_5UTR

206603_at

SLC2A4

17

0.315

6.20E–05

0.301

4.80E–07

0.345

3.18E–06

rs9816196

U3 small nucleolar RNA

0.055

3

45321382

Upstream

1553755_at

NXNL1

19

0.315

6.70E–05

0.237

9.98E–05

0.312

2.82E–05

rs6441911

RIS1

0.055

3

45322523

Flanking_5UTR

1553755_at

NXNL1

19

0.315

6.20E–05

0.245

4.73E–05

0.312

2.82E–05

rs9878275

Probable leucyl–tRNA synthetase

0.055

3

45331043

Upstream

1553755_at

NXNL1

19

0.311

8.31E–05

0.244

5.26E–05

0.312

2.82E–05

rs9846284

U3 small nucleolar RNA

0.055

3

45331970

Upstream

1553755_at

NXNL1

19

0.315

6.20E–05

0.245

4.88E–05

0.312

2.82E–05

rs9850725

LARS2

0.055

3

45332431

Flanking_5UTR

1553755_at

NXNL1

19

0.315

6.20E–05

0.245

4.73E–05

0.312

2.82E–05

rs17564430

IGSF4 (CADM1)

0.155

11

114548784

Flanking_3UTR

206571_s_at

MAP4K4

2

-0.337

1.74E–05

0.237

8.48E–05

-0.322

1.51E–05

rs11215406

IGSF4 (CADM1)

0.138

11

Intron114570292

Intron

206571_s_at

MAP4K4

2

-0.335

1.92E–05

0.248

3.93E–05

-0.322

1.51E–05

rs11215406

IGSF4 (CADM1)

0.138

11

114570292

Intron

204201_s_at

PTPN13

4

-0.335

1.92E–05

0.243

5.49E–05

-0.301

5.30E–05

rs17564430

IGSF4 (CADM1)

0.155

11

114548784

Flanking_3UTR

204880_at

MGMT

10

-0.337

1.74E–05

-0.236

9.07E–05

0.332

7.44E–06

rs17564430

IGSF4 (CADM1)

0.155

11

114548784

Flanking_3UTR

1556095_at

UNC13C

15

-0.337

1.74E–05

0.256

2.21E–05

-0.354

1.60E–06

rs17564430

IGSF4 (CADM1)

0.155

11

114548784

Flanking_3UTR

1556096_s_at

UNC13C

15

-0.337

1.74E–05

0.240

7.07E–05

-0.337

5.47E–06

rs17564430

IGSF4 (CADM1)

0.155

11

114548784

Flanking_3UTR

1569969_a_at

UNC13C

15

-0.337

1.74E–05

0.257

1.93E–05

-0.332

7.56E–06

rs11215406

IGSF4 (CADM1)

0.138

11

114570292

Intron

1556095_at

UNC13C

15

-0.335

1.92E–05

0.276

4.27E–06

-0.354

1.60E–06

rs11215406

IGSF4 (CADM1)

0.138

11

114570292

Intron

1556096_s_at

UNC13C

15

-0.335

1.92E–05

0.255

2.29E–05

-0.337

5.47E–06

rs11215406

IGSF4 (CADM1)

0.138

11

114570292

Intron

1569969_a_at

UNC13C

15

-0.335

1.92E–05

0.270

7.08E–06

-0.332

7.56E–06

rs11215416

IGSF4 (CADM1)

0.147

11

114582537

Intron

1556095_at

UNC13C

15

-0.346

9.57E–06

0.260

1.59E–05

-0.354

1.60E–06

rs11215416

IGSF4 (CADM1)

0.147

11

114582537

Intron

1556096_s_at

UNC13C

15

-0.346

9.57E–06

0.242

6.21E–05

-0.337

5.47E–06

rs11215416

IGSF4 (CADM1)

0.147

11

114582537

Intron

1569969_a_at

UNC13C

15

-0.346

9.57E–06

0.258

1.84E–05

-0.332

7.56E–06

rs2008801

IGSF4 (CADM1)

0.126

11

114513385

Flanking_3UTR

225532_at

CABLES1

18

-0.317

5.42E–05

-0.254

2.54E–05

0.271

2.92E–04

rs2507905

IGSF4 (CADM1)

0.126

11

114513815

Downstream

225532_at

CABLES1

18

-0.317

5.42E–05

-0.254

2.54E–05

0.271

2.92E–04

rs7122402

IGSF4 (CADM1)

0.126

11

114521517

Downstream

225532_at

CABLES1

18

-0.317

5.42E–05

-0.261

1.43E–05

0.271

2.92E–04

rs4938179

IGSF4 (CADM1)

0.132

11

114538635

Downstream

225532_at

CABLES1

18

-0.289

2.56E–04

-0.247

4.34E–05

0.271

2.92E–04

rs17564430

IGSF4 (CADM1)

0.155

11

114548784

Flanking_3UTR

225532_at

CABLES1

18

-0.337

1.74E–05

-0.242

6.19E–05

0.271

2.92E–04

  1. “Integrated analyses” with the top expression probe sets that were associated with SNPs within loci with gemcitabine IC50 (SNP vs. Expression P value <10–4, and Expression vs. IC50 P value < 10–4), except for C3orf23 (SNP vs. Expression P value < 10–4, and Expression vs. IC50 P value ≈ 10–4). Eighteen unique probe sets, representing 12 annotated genes that were associated with 66 SNPs within 7 loci and were significantly correlated with gemcitabine IC50 values are listed. (B) “Integrated analyses” for AraC. Eleven unique probe sets, representing 6 annotated genes that were associated with 15 SNPs within 3 loci and were significantly correlated with AraC IC50 values are listed. R values represent correlation coefficients for each association.