Table 2.
Independent SNPs associated with beverage consumption that met pre-specified replication criteria1
| Locus | Chr:pos | dbSNP ID | Closest gene | EA/RA | EAF | Stage 1 (n = 85 852) | Stage 2 (n = 39 924) | Joint meta-analysis | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Beta2 | SE2 | P | Beta2 | SE2 | P | Beta2 | SE2 | P | N | ||||||
| Total bitter beverages | |||||||||||||||
| 2p23.3 | 2:27730940 | rs1260326 | GCKR | C/T | 0.61 | 1.05 | 0.18 | 2.87E-09 | 1.63 | 0.45 | 3.46E-04 | 1.13 | 0.16 | 8.33E-12 | 125 776 |
| 4q22.1 | 4:89039082 | rs1481012 | ABCG2 | A/G | 0.89 | 1.42 | 0.27 | 2.09E-07 | 2.10 | 0.71 | 3.49E-03 | 1.50 | 0.25 | 3.82E-09 | 125 776 |
| 7p21.1 | 7:17284577 | rs4410790 | AHR | C/T | 0.63 | 2.58 | 0.18 | 2.36E-46 | 3.71 | 0.46 | 3.36E-15 | 2.73 | 0.17 | 7.09E-59 | 125 776 |
| 7q11.23 | 7:75616105 | rs17685 | POR | A/G | 0.28 | 1.35 | 0.19 | 2.71E-12 | 2.50 | 0.50 | 7.64E-07 | 1.50 | 0.18 | 1.02E-16 | 125 776 |
| 15q24.1 | 15:75027880 | rs2472297 | CYP1A1/2 | T/C | 0.26 | 3.42 | 0.19 | 6.58E-67 | 3.42 | 0.54 | 4.74E-10 | 3.43 | 0.18 | 1.81E-75 | 125 776 |
| Bitter non-alcoholic beverages | |||||||||||||||
| 1q21.3 | 1:150956128 | rs12405726 | ANXA9 | A/G | 0.35 | 1.05 | 0.18 | 5.90E-09 | 1.49 | 0.45 | 1.01E-03 | 1.12 | 0.17 | 3.50E-11 | 125 776 |
| 7p21.1 | 7:17284577 | rs4410790 | AHR | C/T | 0.63 | 2.97 | 0.18 | 2.94E-61 | 3.87 | 0.44 | 1.16E-17 | 3.10 | 0.16 | 1.39E-76 | 125 776 |
| 7p21.1 | 7:17401027 | rs7791070 | KCCAT333 | T/C | 0.76 | 1.67 | 0.20 | 2.44E-16 | 2.33 | 0.52 | 8.63E-06 | 1.76 | 0.19 | 2.09E-20 | 125 776 |
| 7q11.23 | 7:73047551 | rs35855035 | MLXIPL | T/C | 0.22 | 1.05 | 0.21 | 4.71E-07 | 1.47 | 0.53 | 5.43E-03 | 1.11 | 0.19 | 1.15E-08 | 125 776 |
| 7q11.23 | 7:75615006 | rs1057868 | POR | T/C | 0.29 | 1.71 | 0.19 | 5.17E-19 | 2.41 | 0.47 | 5.50E-07 | 1.81 | 0.18 | 3.95E-24 | 125 776 |
| 15q24.1 | 15:75027880 | rs2472297 | CYP1A1/2 | T/C | 0.26 | 3.93 | 0.19 | 1.30E-87 | 3.88 | 0.52 | 3.04E-13 | 3.93 | 0.18 | 2.20E-99 | 125 776 |
| 22q13.2 | 22:41958862 | rs9607819 | CSDC2 | G/C | 0.81 | 1.29 | 0.22 | 4.56E-09 | 1.45 | 0.54 | 7.43E-03 | 1.31 | 0.20 | 1.20E-10 | 125 776 |
| Bitter alcoholic beverages 3 | |||||||||||||||
| 2p23.3 | 2:27730940 | rs1260326 | GCKR | C/T | 0.61 | 1.41 | 0.11 | 2.78E-34 | 0.87 | 0.24 | 2.87E-04 | 1.31 | 0.10 | 2.52E-36 | 376 372 |
| 4p14 | 4:39414993 | rs11940694 | KLB | G/A | 0.60 | 1.34 | 0.12 | 1.07E-30 | 0.92 | 0.24 | 1.37E-04 | 1.26 | 0.10 | 2.25E-33 | 376 372 |
| 4q23 | 4:100239319 | rs1229984 | ADH1B | C/T | 0.98 | 10.43 | 0.38 | 1.08E-151 | 3.60 | 0.64 | 2.48E-08 | 8.60 | 0.32 | 2.00E-142 | 376 372 |
| 11p11.2 | 11:47722819 | rs7935528 | AGBL2 | A/G | 0.45 | 0.75 | 0.11 | 2.83E-11 | 0.71 | 0.24 | 3.12E-03 | 0.74 | 0.10 | 3.33E-13 | 376 372 |
| Coffee 4 | |||||||||||||||
| 1q25.2 | 1:177873210 | rs574367 | SEC16B | T/G | 0.21 | 0.99 | 0.19 | 2.61E-07 | 1.62 | 0.58 | 5.19E-03 | 1.05 | 0.18 | 8.06E-09 | 375 833 |
| 2p25.3 | 2:631606 | rs10865548 | TMEM18 | G/A | 0.83 | 1.52 | 0.21 | 2.35E-13 | 1.66 | 0.59 | 5.11E-03 | 1.54 | 0.19 | 4.46E-15 | 375 833 |
| 2p23.3 | 2:27730940 | rs1260326 | GCKR | C/T | 0.61 | 1.31 | 0.16 | 2.92E-16 | 1.79 | 0.46 | 1.22E-04 | 1.36 | 0.15 | 2.62E-19 | 375 833 |
| 7p21.1 | 7:172776925 | rs117692895 | AHR | C/G | 0.01 | 4.01 | 0.71 | 2.60E-08 | 7.12 | 2.23 | 1.86E-03 | 4.29 | 0.67 | 4.13E-10 | 374 046 |
| 7p21.1 | 7:17284577 | rs4410790 | AHR | C/T | 0.63 | 3.85 | 0.16 | 4.73E-121 | 4.63 | 0.47 | 4.20E-22 | 3.94 | 0.15 | 5.59E-141 | 375 833 |
| 7p21.1 | 7:17334899 | rs4719497 | AHR | T/C | 0.87 | 1.12 | 0.23 | 1.10E-06 | 1.81 | 0.67 | 7.27E-03 | 1.20 | 0.22 | 4.23E-08 | 375 833 |
| 7p21.1 | 7:17443199 | rs12699844 | KCCAT333 | C/T | 0.47 | 1.22 | 0.16 | 1.16E-14 | 1.37 | 0.46 | 2.93E-03 | 1.24 | 0.15 | 1.35E-16 | 375 833 |
| 7p21.1 | 7:17562952 | rs73073176 | LOC101927630 | C/T | 0.87 | 2.30 | 0.23 | 1.54E-22 | 2.34 | 0.69 | 8.47E-04 | 2.31 | 0.22 | 5.56E-25 | 375 833 |
| 7q11.23 | 7:73037956 | rs34060476 | MLXIPL | G/A | 0.13 | 1.79 | 0.23 | 8.05E-15 | 2.78 | 0.68 | 5.23E-05 | 1.89 | 0.22 | 5.06E-18 | 375 833 |
| 7q11.23 | 7:75615006 | rs1057868 | POR | T/C | 0.29 | 1.88 | 0.17 | 2.44E-27 | 2.72 | 0.50 | 1.09E-07 | 1.97 | 0.16 | 5.26E-33 | 375 833 |
| 11q12.1 | 11:56272114 | rs597045 | OR8U8 | A/T | 0.69 | 1.02 | 0.17 | 2.86E-09 | 1.41 | 0.50 | 4.98E-03 | 1.07 | 0.16 | 6.62E-11 | 375 833 |
| 14q12 | 14:33075243 | rs1956218 | AKAP6 | G/A | 0.56 | 0.77 | 0.16 | 1.27E-06 | 1.30 | 0.45 | 4.52E-03 | 0.82 | 0.15 | 3.62E-08 | 375 833 |
| 15q24.1 | 15:75027880 | rs2472297 | CYP1A1/2 | T/C | 0.27 | 4.54 | 0.18 | 8.28E-141 | 4.57 | 0.56 | 8.69E-16 | 4.54 | 0.17 | 5.19E-155 | 375 833 |
| 18q21.32 | 18:57808978 | rs66723169 | MC4R | A/C | 0.23 | 1.41 | 0.19 | 3.32E-14 | 1.91 | 0.54 | 4.82E-04 | 1.47 | 0.18 | 9.88E-17 | 375 833 |
| 22q11.23 | 22:24747031 | rs2330783 | SPECC1L-ADORA2A | G/T | 0.99 | 4.44 | 0.67 | 6.20E-11 | 5.25 | 1.91 | 6.72E-03 | 4.53 | 0.63 | 1.57E-12 | 375 833 |
| SSBs | |||||||||||||||
| 16q12.2 | 16:53809123 | rs55872725 | FTO | C/T6 | 0.59 | 0.96 | 0.15 | 1.29E-10 | 1.28 | 0.21 | 6.36E-10 | 1.07 | 0.12 | 1.05E-18 | 125 776 |
Chr:pos, chromosome:position. EA, effect allele; EAF, effect allele frequency; RA, reference allele; SE, standard error.
1Independent SNPs were identified using conditional analysis. Independent SNPs with P < 5 × 10−6 in stage 1 were replicated if (i) stage 2 P < 0.01; (ii) joint stage 1 and stage 2 meta-analysis P < 5 × 10−8; and (iii) consistent direction of effect.
2Betas and SEs are interpreted as % change per allele.
3 n = 336 448 in stage 1.
4 n = 335 909 in stage 1.
5 n = 38 137 in stage 2.
6T allele is the BMI increasing allele.