Table 2.
Association results for novel SNVs identified in the combined meta-analysis of the discovery and replication cohorts
| 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) | |
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
Bold font highlights the genome-wide significant P-values from the meta-analysis of discovery plus replication studies