Genetic Variants Associated with Chronic Obstructive Pulmonary Disease Risk: Cumulative Epidemiological Evidence from Meta-Analyses and Genome-Wide Association Studies

Table 1

Statistically significant variants from meta-analyses, false-positive report probabilities (FPRP), and cumulative epidemiological evidence.

Gene

Variants

Year

Comparison

Ethnicity

OR (95% CI)

Adjustment for smoking

Publication bias/heterogeneity

I^2 (%)

No. of studies

Cases/control

Maf (%)^†

Number of test alleles or genotypes

Venice criteria

Power OR of 1.5

FPRP values at prior probability of 0.01

Cumulative epidemiological evidence

Reference

PI

PIMZ

2004

PIMZ vs PIMM

Diverse

2.31 (1.60–3.35)

No

0.15/0.002

58.6

16

3653/12340

4.43

822

BCC^‡

0.011

0.081

Weak

[30]

PIMZ vs PIMM

Diverse

1.61 (0.92–2.81)

Yes

No/0.15

NA

5

1600/7645

—

—

—

—

—

—

[30]

PI

PISZ

2005

PISZ vs PIMM

Diverse

3.26 (1.24–8.57)

No

0.98/0.23

27.2

6

2404/8999

0.12

42

NBC^‡

0.058

0.966

Weak

[31]

PI

PIMS

2005

PIMS vs PIMM

Diverse

1.19 (1.02–1.38)

No

1.0/0.54

0.0

17

3630/13030

7.26

1169

AAA

0.999

0.679

Moderate

[31]

PIMS vs PIMM

Diverse

1.02 (0.81–1.28)

Yes

NA/NA

NA

5

1526/7859

—

—

—

—

—

—

[31]

GSTM1

Null/present

2018

Null vs present

Diverse

1.52 (1.31–1.77)

No

No/<0.00001

64.0

37

4669/4914

46.99

5018

ACA

0.432

0.000

Moderate

[32]

Null vs present

Asian

1.59 (1.29–1.96)

No

No/<0.0001

64.0

23

2374/2630

44.79

2531

ACA

0.293

0.005

Moderate

[32]

Null vs present

Caucasian

1.27 (1.11–1.44)

No

No/0.03

49.0

11

1881/1938

49.85

2045

ABA

0.995

0.019

Strong

[32]

GSTT1

Null/present

2018

Null vs present

Diverse

1.28 (1.09–1.50)

No

No/0.001

51.0

29

3273/3578

32.36

2338

ACA

0.975

0.188

Weak

[32]

Null vs present

Asian

1.30 (1.05–1.61)

No

No/0.002

57.0

18

2025/2253

39.61

1697

ACA

0.905

0.639

Weak

[32]

TGF-b1

rs1800470

2011

C vs T

Diverse

0.82 (0.70–0.96)

No

0.326/0.01

57.6

10

1507/2542

43.14

3533

ACA

0.995

0.575

Weak

[33]

C vs T

Caucasian

0.77 (0.60–0.98)

No

No/0.02

65.9

5

840/1788

41.11

2061

ACA

0.879

0.791

Weak

[33]

TGF-β1

rs1982073※

2017

C vs T

Caucasian

0.79 (0.64–0.99)

No

No/0.006

75.7

4

1656/2564

40.72

3348

ACA

0.930

0.812

Weak

[34]

IL1RN

rs2234663

2019

L vs 2

Diverse

0.56 (0.39–0.80)

No

0.02/0.25

30.3

5

322/365

10.11

171

BBC^‡

0.169

0.458

Weak

[35]

IL-6

rs1800796

2019

CC + GC vs GG

Diverse

2.23 (1.46–3.40)

No

0.05/0.38

19.3

3

574/862

26.33

511

BAC^‡

0.033

0.370

Weak

[35]

IL-13

rs1800925

2017

C vs T

Diverse

1.57 (1.21–2.04)

No

No/0.015

57.9

9

1477/891

16.27

963

BCA

0.366

0.166

Weak

[36]

C vs T

Asian

1.88 (1.23–2.87)

No

0.268/0.016

67.1

5

555/544

14.71

425

BCA

0.148

0.698

Weak

[36]

C vs T

Caucasian

1.30 (1.01–1.67)

No

0.644/0.314

15.6

4

922/347

18.73

538

BAA

0.869

0.820

Weak

[36]

IL-27

rs153109

2016

G vs A

Asian

0.51 (0.34–0.74)

No

NA/NA

NA

1

120/100

45.50

NA

XXX

0.079

0.329

NA

[37]

MMP-9

rs3918242

2017

T vs C

Diverse

1.32 (1.02–1.71)

No

0.12/<0.001

77.0

13

2295/2539

11.17

1408

ACA

0.833

0.808

Weak

[38]

CT + TT vs CC

Asian

1.80 (1.04–3.11)

No

No/<0.001

85.0

8

1101/1147

14.34

645

BCA

0.257

0.931

Weak

[38]

MMP-12

rs652438

2014

G vs A

Diverse

1.62 (1.08–2.42)

No

>0.05/0.070

57.5

4

710/1652

10.57

328

BCA

0.354

0.838

Weak

[39]

CHRNA

rs16969968

2014

C vs T

Diverse

1.27 (1.17–1.39)

No

No/0.655

0.0

3

1996/6463

29.42

4979

AAA

1.000

0.000

Strong

[40]

CHRNA

rs1051730

2014

T vs C

Diverse

1.14 (1.10–1.18)

No

No/0.318

14.0

9

10466/39054

30.80

30264

AAA^§

1.000

0.000

Strong

[40]

T vs C

Non-Asian

1.14 (1.10–1.18)

No

No/0.124

42.2

6

8620/37099

32.32

30088

ABA^§

1.000

0.000

Strong

[40]

CHRNA

rs8034191

2014

C vs T

Diverse

1.29 (1.18–1.41)

No

No/0.644

0.0

5

2652/2565

24.09

2933

AAA

1.000

0.000

Strong

[40]

CHRNA

rs6495309

2014

C vs T

Diverse

1.26 (1.09–1.45)

No

Pre/0.109

50.4

4

1977/2131

48.12

3756

ACC

0.993

0.112

Weak

[40]

ADAM33

rs3918396

2014

GG + AG vs AA

Diverse

1.42 (1.12–1.79)

No

0.168/0.89

0.0

6

1422/3034

25.61

3806

AAA

0.679

0.304

Moderate

[41]

GG + AG vs AA

Asian

1.45 (1.14–1.85)

No

NA/0.665

0.0

3

642/630

67.38

645

BAX

0.607

0.313

NA

[41]

GG + AG vs AA

Diverse

1.45 (1.14–1.84)

Yes

No/0.91

0.0

3

836/848

54.07

1052

AAA

0.610

0.266

Moderate

[41]

ADAM33

rs597980

2014

A vs G

Caucasian

1.25 (1.05–1.48)

No

NA/0.158

49.9

2

296/2294

40.87

2148

ABX

0.983

0.492

NA

[42]

ADAM33

rs2280091

2014

GG vs AA + AG

Diverse

1.76 (1.27–2.43)

No

0.483/0.348

10.5

8

2112/3952

13.18

197

BAA

0.166

0.262

Weak

[42]

G vs A

Asian

2.03 (1.40–2.94)

No

0.857/0.006

76.0

4

1130/1135

13.04

798

BCA

0.055

0.245

Weak

[42]

ADAM33

rs511898

2019

A vs G

Diverse

1.16 (1.04–1.30)

No

0.726/0.048

44.5

12

2454/4481

33.17

4763

ABA

1.000

0.514

Weak

[51]

ADAM33

rs612709

2014

A vs G

Diverse

0.60 (0.52–0.68)

No

0.070/0.107

44.7

6

1341/3359

67.61

5345

ABA

0.050

0.000

Strong

[42]

A vs G

Asian

0.61 (0.42–0.89)

No

0.256/0.021

74.1

3

767/763

26.54

664

BCA

0.322

0.760

Weak

[42]

A vs G

Caucasian

0.64 (0.53–0.77)

No

0.324/0.798

0.0

3

574/2596

79.68

4681

AAA

0.333

0.001

Strong

[42]

ADAM33

rs2280090※

2014

A vs G

Asian

0.46 (0.33–0.66)

No

0.581/0.021

74.1

3

767/763

32.31

763

BCA

0.022

0.101

Weak

[42]

CYP1A1

rs4646903

2015

CC vs TT

Diverse

1.73 (1.18–2.55)

No

No/0.34

11.0

5

532/591

23.43

141

BAA

0.236

0.703

Weak

[43]

CC vs TT

Asian

1.84 (1.11–3.06)

No

NA/0.65

0.0

2

158/154

35.27

88

CAX

0.216

0.896

NA

[43]

CYP1A1

rs1048943

2015

GG vs AA

Diverse

3.23 (1.50–6.93)

No

No/0.16

45.0

3

510/553

9.01

41

CBA

0.024

0.914

Weak

[43]

SP-A

Common polymorphisms

2013

W vs M

Diverse

1.53 (1.14–2.05)

No

>0.05/0.043

56.5

3

383/369

23.83

828

BCA

0.447

0.493

Weak

[44]

SP-D

rs721917

2019

T vs C

Diverse

1.39 (1.18–1.65)

No

0.375/0.901

0.0

5

561/550

45.36

1106

AAA

0.808

0.020

Strong

[45]

T vs C

Asian

1.44 (1.20–1.73)

No

0.457/0.978

0.0

4

499/435

43.56

917

BAA

0.669

0.014

Strong

[45]

SP-A/B/D

Common polymorphisms

2013

W vs M

Asian

1.43 (1.15–1.78)

No

>0.05/0.001

71.3

4

485/488

27.28

1080

ACA

0.666

0.169

Weak

[44]

TNF-α

rs1800629

2016

A vs G

Diverse

1.56 (1.29–1.89)

No

No/0.000

70.8

38

3951/5110

10.96

2326

ACA

0.344

0.002

Moderate

[46]

A vs G

Asian

2.40 (1.98–2.90)

No

No/0.093

29.8

22

2067/2167

7.63

1011

ABA

0.000

0.000

Strong

[46]

A vs G

Diverse

1.13 (0.95–1.35)

Yes

No/0.089

34.9

15

1500/1239

—

—

—

—

—

—

[46]

A vs G

Asian

1.26 (0.69–2.30)

Yes

No/0.063

52.2

6

570/616

—

—

—

—

—

—

[46]

TNF-α

rs1800630

2013

A vs C

Diverse

0.76 (0.60–0.97)

No

No/0.158

42.3

4

606/622

16.64

155

BBA

0.854

0.761

Weak

[47]

A vs C

Asian

0.56 (0.37–0.85)

No

NA/0.640

0.0

2

202/203

16.50

40

CAX

0.206

0.756

NA

[47]

EPHX1

rs1051740

2012

CC vs TT

Diverse

1.33 (1.06–1.69)

No

0.158/<0.0001

73.0

25

4808/24888

52.59

5186

ACA

0.837

0.699

Weak

[48]

CC vs TT

Caucasian

1.61 (1.12–2.31)

No

No/<0.0001

81.0

12

3930/23907

49.91

4343

ACA

0.350

0.733

Weak

[48]

EPHX1

rs2234922

2012

Extremely slow vs normal

Diverse

1.77 (1.23–2.55)

No

No/<0.0001

76.0

15

3146/21391

NA

4180

ACA

0.187

0.535

Weak

[48]

Slow vs normal

Diverse

1.44 (1.13–1.85)

No

No/<0.00001

74.0

15

4248/28597

NA

12488

ACA

0.625

0.407

Weak

[48]

Extremely slow vs normal

Caucasian

2.64 (1.30–5.38)

No

No/<0.0001

85.0

8

2685/20884

NA

3813

ACA

0.060

0.926

Weak

[48]

Slow vs normal

Caucasian

1.31 (1.01–1.71)

No

No/0.01

62.0

8

3563/27956

NA

11763

ACA

0.840

0.847

Weak

[48]

VDBP

1F

2015

1F vs 1S

Diverse

1.47 (1.22–1.77)

No

No/0.447

0.0

8

809/1407

20.47

1125

AAA

0.584

0.008

Strong

[49]

1F vs 1S

Asian

1.53 (1.22–1.92)

No

0.133/0.935

0.0

5

510/460

30.84

319

BAA

0.432

0.052

Moderate

[49]

VDBP

1S

2015

1S vs non 1S

Diverse

0.86 (0.77–0.96)

No

No/0.12

35.0

11

1410/1595

46.14

2578

ABA

1.000

0.416

Weak

[50]

1S vs non 1S

Asian

0.76 (0.64–0.89)

No

No/0.23

26.0

7

785/719

31.71

869

BBA

0.948

0.064

Moderate

[50]

HHIP

rs13118928

2019

G vs A

Diverse

1.14 (1.08–1.20)

No

No/0.930

0.0

7

5157/9768

36.39

10250

AAA^§

1.000

0.000

Strong

[57]

COX2

rs20417

2014

C vs G

Diverse

1.33 (1.06–1.67)

No

>0.05/0.209

30.2

6

930/719

17.04

597

BBA

0.850

0.621

Weak

[39]

IREB2

rs2568494

2016

AA vs GG + AG

Diverse

1.38 (1.09–1.76）

No

No/0.171

40.1

4

2001/2167

22.70

322

BBA

0.749

0.555

Weak

[52]

HMOX1

L allele

2017

L vs S + M

Diverse

2.02 (1.31–3.11)

No

0.79/0.08

52.0

5

601/547

8.78

287

BCB

0.088

0.612

Weak

[53]

L vs S + M

Asian

2.23 (1.68–2.95)

No

No/0.46

0.0

4

471/452

9.29

262

BAB

0.003

0.001

Strong

[53]

ACE

I/D※

2018

D vs I

Asian

1.63 (1.17–2.27)

No

No/0.065

54.7

5

380/206

39.86

685

BCA

0.311

0.549

Weak

[54]

ADRB2

rs1042714※

2018

G vs C

Asian

1.29 (1.02–1.65)

No

0.970/0.34

10.0

4

613/587

11.46

314

BAA

0.885

0.826

Weak

[55]

FAM13A

rs7671167

2017

CC + CT vs TT

Diverse

0.76 (0.62–0.94)

No

No/0.002

71.0

7

3571/4344

53.96

5892

ACA

0.887

0.560

Weak

[56]

CC + CT vs TT

Caucasian

0.63 (0.43–0.93)

No

NA/0.12

59.0

2

607/1009

52.73

1216

ACX

0.388

0.837

NA

[56]

NA: not available; No: significant publication bias was not found; present: significant publication bias was found; W vs M: wild allele vs mutant allele. ^†Frequency of minor allele in controls. ^‡The grade of C is assigned to protection from bias because the sensitivity analysis indicated that the significant summary OR can be substantially changed. ^§The grade of A is assigned to protection from bias though the OR is less than 1.15, and the association is replicated by GWAS. ^¶Frequency less than 1%, the amount of evidence is not applied considering an A grade is unlikely to obtain. ^※Reported nonsignificantly in the diverse populations, but significant results were reported in the stratified analysis by ethnicity. value or I² was calculated according to the original data provided in the article with Stata 12.0 since the article did not present these values. value of Egger’s test/test for between-study heterogeneity.