Table 2 Association results for novel SNVs identified in the combined meta-analysis of the discovery and replication cohorts

From: Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

dbSNP ID (Exome-chip ID)

Chr:Pos

EA/OA

Gene

Consequence

Trait

EAF

Beta (se) in replication stage

P-value in combined meta-analysis

(P-value in Discovery/Replication stage)

Notes

Combining only genotyped Exome-chip content on the Axiom array

rs1514175

1:74991644

G/A

TNNI3K

Intronic

SI

0.57

−0.011 (0.003)

5.42 × 10−9 (9.03 x 10−5/1.0 x 10−5)

Previously associated with BMI

rs7096169

10:104618695

G/A

BORCS7

(CNNM2# in Table 1)

Intronic

SI

0.31

0.016 (0.003)

2.17 × 10−13 (3.38 × 10−7/7.3 × 10−9)

r2 = 0.28 between rs7096169 and rs12780116 (Table 1) in 1000 Genomes EUR. Previously associated with Schizophrenia. rs7096169 an eQTL for ARL3, BORCS7, and AS3MT in ≥1 of the brain tissues in GTEx

rs2292239

12:56482180

G/T

ERBB3

Intronic

SI

0.66

0.0121 (0.003)

2.78 × 10−8 (7.56 × 10−5/1.5 × 10−5)

Previously associated with type-1 diabetes and years of educational attainment. rs2292239 is an eQTL for RPS26 and SUOX in ≥4 of the brain tissues in GTEx

rs216195

17:2203167

G/T

SMG6#

Missense

SI

0.29

−0.0076 (0.003)

2.41 × 10−9 (2.80 × 10−8/8.5 × 10−3)

Same SNV as in Table 1

Combining well-imputed Exome-chip content on the Axiom array

rs2960306 (exm383568)

4:2990499

T/G

GRK4

Missense

CPD

0.34

−0.024 (0.005)

1.06 × 10−9 (3.99 × 10−5/3.8 × 10−6)

rs2960306 is an eQTL for GRK4 in four of the brain tissues in GTEx

rs4908760

1:8526142

A/G

RERE

Intronic

SI

0.35

0.0078 (0.003)

1.76 × 10−8 (3.36 × 10−6/4.7 × 10−3)

Previously associated with Vitiligo

rs6692219 (exm127721)

1:179989584

C/G

CEP350

Missense

SI

0.028

−0.0257 (0.008)

4.69 × 10−9 (1.08 × 10−6/1.3 × 10−3)

 

rs11971186

7:126437897

G/A

GRM8

Intronic

SI

0.20

−0.0080 (0.003)

1.45 × 10−8 (1.38 × 10−6/3.9 × 10−3)

 

rs150493199 (exm249655)

2:179721072

A/T

CCDC141

Missense

SC

0.0098

0.048 (0.134)

1.28 × 10−8 (6.45 × 10−8/0.72)

 

Non-Exome-chip SNVs

rs3001723

1:44037685

A/G

PTPRF

Intronic

SI

0.21

0.0159 (0.003)

6.64 × 10−11 (0.00015/4.1 × 10−8)

Previously associated with Schizophrenia and Years of educational attainment

rs1937455

1:66416939

G/A

PDE4B

Intronic

SI

0.30

−0.0146 (0.0027)

1.23 × 10−9 (0.00073/5.6 × 10−8)

 

rs72720396

1:91191582

G/A

BARHL2

Intergenic

SI

0.16

−0.0150 (0.003)

9.86 x 10−9 (5.63 × 10−5/1.9 × 10−6)

 

rs6673752

1:154219177

C/G

UBAP2L

Intronic

SI

0.055

−0.027 (0.004)

1.1 × 10−11 (NA/1.1 × 10−11)

 

rs2947411

2:614168

G/A

TMEM18

Intergenic

SI

0.83

0.0189 (0.004)

4.97 × 10−10 (0.00017/7.1 × 10−8)

Previously associated with BMI

rs528301

2:45154908

A/G

SIX3

Intergenic

SI

0.38

0.0136 (0.002)

4.12 × 10−11 (1.77 × 10−6/3.8 × 10−7)

 

rs6738833

2:104150891

T/C

TMEM182#

Intergenic

SI

0.33

−0.018 (0.003)

8.66 × 10−14 (1.63 × 10−6/4.4 × 10−11)

r2 = 0.69 between rs6738833 and rs12616219 (Table 1) in European samples of the 1000 Genomes Project

rs13026471

2:137564022

T/C

THSD7B

Intronic

SI

0.18

0.0127 (0.003)

2.45 × 10−8 (0.00028/3.0 x 10−5)

 

rs6724928

2:156005991

C/T

KCNJ3

Intergenic

SI

0.32

−0.011 (0.003)

4.47 × 10−8 (0.0019/4.8 × 10−5)

 

rs13022438

2:162800372

G/A

SLC4A10

Intronic

SI

0.27

0.0146 (0.003)

1.41 × 10−11 (0.0005/8.1 × 10−8)

 

rs1869244

3:5724531

A/G

LOC105376939

Intergenic

SI

0.32

0.0123 (0.003)

2.76 × 10−9 (0.00040/4.1 x 10−6)

 

rs35438712

3:85588205

T/C

CADM2

Intronic

SI

0.25

0.017 (0.003)

1.99 × 10−13 (1.15 × 10−5/3.2 × 10−10)

 

rs6883351

5:22193967

T/C

CDH12

Intronic

SI

0.34

0.0129 (0.003)

4.69 × 10−8 (0.0010/1.4 × 10−6)

 

rs6414946

5:87729711

C/A

TMEM161B

Intronic

SI

0.32

−0.0137 (0.003)

5.27 × 10−10 (3.63 × 10−5/2.8 × 10−7)

 

rs11747772

5:166992708

C/T

TENM2

Intronic

SI

0.25

0.0144 (0.003)

6.20 × 10−9 (0.011/2.2 × 10−7)

 

rs9320995

6:98726381

G/A

POU3F2

Intergenic

SI

0.18

0.0150 (0.003)

1.70 × 10−8 (0.00079/6.1 × 10−7)

 

rs10255516

7:1675621

G/A

ELFN1

Intergenic

SI

0.33

−0.0139 (0.003)

2.86 × 10−10 (0.0021/1.8 × 10−7)

 

rs10807839

7:3344629

G/A

SDK1

Intronic

SI

0.19

0.0162 (0.003)

8.93 × 10−11 (0.0026/4.4 × 10−8)

 

rs6965740

7:117514840

T/G

CTTNBP2

Intergenic

SI

0.31

−0.0126 (0.003)

9.66 × 10−9 (5.56 × 10−6/2.8 × 10−6)

 

rs11776293

8:27418429

T/C

EPHX2

Intronic

SI

0.12

−0.0200 (0.003)

2.23 × 10−12 (0.00011/8.9 × 10−9)

rs11776293 is an eQTL for CHRNA2 in cerebellum in GTEx

rs1562612

8:59817068

G/A

TOX

Intronic

SI

0.35

−0.0112 (0.003)

1.15 × 10−9 (1.42 × 10−5/2.9 × 10−5)

 

rs3857914

8:93184065

C/T

RUNX1T1

Intergenic

SI

0.19

0.0157 (0.003)

1.54 × 10−9 (0.065/7.1 × 10−8)

 

rs2799849

9:86752641

C/T

RMI1

Intergenic

SI

0.22

−0.0156 (0.003)

1.94 × 10−8 (0.026/4.8 × 10−8)

 

rs6482190

10:22037809

A/G

LOC107984214

Intronic

SI

0.17

0.0146 (0.003)

8.85 × 10−9 (0.0021/9.5 × 10−7)

 

rs4523689

11:7950797

G/A

OR10A6

Intergenic

SI

0.27

−0.012 (0.003)

7.77 × 10−9 (0.00030/2.2 × 10−5)

 

rs933006

13:38350193

A/G

TRPC4

Intronic

SI

0.32

−0.0143 (0.003)

3.50 × 10−8 (0.022/9.6 × 10−8)

 

rs557899

15:47643795

A/C

SEMA6D

Intronic

SI

0.26

0.0157 (0.003)

2.99 × 10−13 (4.46 × 10−5/1.0 × 10−8)

 

rs76608582

19:4474725

A/C

HDGFRP2

Intronic

SI

0.029

−0.0360 (0.007)

8.50 × 10−9 (0.012/4.3 × 10−8)

 
  1. Chromosome (Chr) and position (Pos) for each SNV is given for hg19 build 37. Only SNVs reaching genome-wide significance (P < 5 × 10-8, in bold) in the combined meta-analysis are shown. Magnitude of the effect size estimates are not presented as traits were transformed in differently by the three consortia analysed. SNVs identified in the discovery stage of this study (see Table 1) are denoted #. The discovery sample size for smoking initiation (SI), CPD, pack-years (PY), and smoking cessation (SC) were 346,813, 128,746, 131,892, and 121,543, respectively; and the replication sample size for SI, CPD, PY, and SC were 275,596, 80,015, 78,897, and 123,851, respectively. NB: rs6673752 (intronic to UBAP2L) was not available in the discovery cohorts. EA effect allele, OA other allele, Beta(se) beta and standard error for association in the replication stage. All SNVs had heterogeneity P > 0.0001
  2. Bold font highlights the genome-wide significant P-values from the meta-analysis of discovery plus replication studies
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