Table 1. Association results for markers from the 14 novel NSCLP risk loci at each stage.
| loci | SNP | BP (hg19) | Alleles* |
NSCLP GWAS (above) and NSCLP replication (below) |
NSCLP Meta |
NSCLO replication (above) and NSCPO replication (below) |
NSCL/P replication 1 |
NSCL/P replication 2 (above) and NSCL/P replication 3 (below) |
1000 Genomes |
|||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F_A | F_U | P | OR | P(F) | OR(F) | F_A | F_U | P | OR | F_A | F_U | P | OR | MAF | P | RR | MAF_CHB | MAF_EUR | ||||
| 2p25.1 | rs287980 | 9971366 | G/A | 0.23 | 0.27 | 1.99E−05 | 0.82 | 1.94E−08 | 0.83 | 0.25 | 0.26 | 2.34E−01 | 0.93 | 0.20 | 0.21 | 5.34E−01 | 0.94 | 0.26 | 4.63E−01 | 0.94 | 0.28 | 0.22 |
| 0.23 | 0.27 | 5.54E−04 | 0.84 | 0.27 | 0.26 | 7.87E−01 | 1.02 | 0.21 | 7.62E−01 | 0.97 | ||||||||||||
| 2p25.1 | rs287982 | 9972442 | G/A | 0.23 | 0.27 | 1.58E−05 | 0.82 | 6.15E−09 | 0.82 | 0.25 | 0.26 | 1.65E−01 | 0.92 | 0.20 | 0.21 | 5.21E−01 | 0.94 | 0.26 | 4.63E−01 | 0.94 | 0.28 | 0.22 |
| 0.23 | 0.27 | 2.28E−04 | 0.83 | 0.27 | 0.26 | 7.63E−01 | 1.02 | 0.21 | 6.85E−01 | 0.96 | ||||||||||||
| 4p16.2 | rs34246903 | 4794195 | C/A | 0.38 | 0.43 | 2.57E−05 | 0.82 | 4.45E−08 | 0.85 | 0.40 | 0.42 | 2.91E−01 | 0.95 | 0.30 | 0.34 | 2.39E−02 | 0.82 | 0.42 | 2.54E−02 | 0.85 | 0.41 | 0.33 |
| 0.40 | 0.43 | 1.09E−02 | 0.89 | 0.41 | 0.42 | 7.77E−01 | 0.99 | 0.33 | 1.65E−01 | 1.13 | ||||||||||||
| 4p16.2 | rs1907989 | 4818925 | A/G | 0.46 | 0.51 | 2.29E−06 | 0.81 | 1.58E−08 | 0.85 | 0.48 | 0.50 | 6.42E−02 | 0.91 | 0.57 | 0.61 | 1.92E−02 | 0.83 | 0.49 | 3.91E−03 | 1.22 | 0.52 | 0.64 |
| 0.48 | 0.50 | 1.94E−02 | 0.90 | 0.50 | 0.50 | 5.78E−01 | 1.03 | 0.36 | 5.14E−01 | 1.06 | ||||||||||||
| 4q28.1 | rs908822 | 124906257 | A/G | 0.10 | 0.07 | 6.13E−07 | 1.46 | 4.33E−08 | 1.31 | 0.09 | 0.08 | 7.64E−02 | 1.17 | 0.08 | 0.07 | 2.44E−01 | 1.20 | 0.08 | 7.14E−03 | 1.41 | 0.07 | 0.06 |
| 0.10 | 0.09 | 4.46E−02 | 1.16 | 0.09 | 0.08 | 5.21E−01 | 1.06 | 0.07 | 3.80E−01 | 1.15 | ||||||||||||
| 5p12 | rs10462065 | 44068846 | A/C | 0.24 | 0.20 | 3.51E−07 | 1.26 | 1.12E−08 | 1.22 | 0.24 | 0.22 | 7.92E−02 | 1.11 | 0.11 | 0.11 | 7.28E−01 | 0.96 | 0.24 | 3.01E−02 | 1.19 | 0.19 | 0.10 |
| 0.23 | 0.20 | 2.04E−03 | 1.18 | 0.22 | 0.22 | 7.17E−01 | 0.98 | 0.12 | 6.66E–01 | 1.05 | ||||||||||||
| 6p24.3 | rs9381107 | 9469238 | A/G | 0.31 | 0.37 | 1.97E−09 | 0.79 | 2.72E−09 | 0.83 | 0.32 | 0.35 | 4.79E−02 | 0.90 | 0.16 | 0.18 | 1.43E−01 | 0.85 | 0.32 | 8.43E−01 | 1.02 | 0.33 | 0.16 |
| 0.33 | 0.36 | 1.40E−02 | 0.89 | 0.34 | 0.35 | 2.81E−01 | 0.95 | 0.15 | 7.75E−01 | 0.97 | ||||||||||||
| 8p11.23 | rs13317 | 38269514 | G/A | 0.30 | 0.34 | 4.10E−06 | 0.83 | 3.96E−08 | 0.85 | 0.31 | 0.33 | 7.59E−02 | 0.91 | 0.21 | 0.22 | 4.46E−01 | 0.93 | 0.31 | 2.65E−01 | 0.92 | 0.39 | 0.25 |
| 0.32 | 0.35 | 7.43E−03 | 0.88 | 0.32 | 0.33 | 3.83E−01 | 0.95 | 0.23 | 3.17E−03 | 0.76 | ||||||||||||
| 8q22.1 | rs12681366 | 95401265 | G/A | 0.44 | 0.49 | 2.95E−06 | 0.82 | 2.35E−10 | 0.83 | 0.46 | 0.48 | 6.16E−02 | 0.91 | 0.32 | 0.34 | 3.01E−01 | 0.92 | 0.45 | 5.62E−01 | 0.96 | 0.48 | 0.35 |
| 0.44 | 0.48 | 2.48E−04 | 0.85 | 0.47 | 0.48 | 4.01E−01 | 0.96 | 0.31 | 2.28E−01 | 0.90 | ||||||||||||
| 8q22.1 | rs957448 | 95541302 | G/A | 0.44 | 0.50 | 3.78E−10 | 0.78 | 9.60E−13 | 0.81 | 0.47 | 0.49 | 5.72E−02 | 0.91 | 0.23 | 0.26 | 1.49E−01 | 0.87 | 0.47 | 1.18E−01 | 0.90 | 0.51 | 0.31 |
| 0.46 | 0.49 | 7.59E−04 | 0.86 | 0.48 | 0.49 | 1.33E−01 | 0.93 | 0.23 | 4.07E−01 | 0.92 | ||||||||||||
| 9q22.32 | rs10512248 | 98259703 | C/A | 0.29 | 0.34 | 1.80E−07 | 0.79 | 5.10E−10 | 0.82 | 0.33 | 0.35 | 4.47E−02 | 0.90 | 0.34 | 0.33 | 4.34E−01 | 1.07 | 0.28 | 1.41E−02 | 0.81 | 0.31 | 0.32 |
| 0.30 | 0.33 | 3.19E−03 | 0.87 | 0.31 | 0.35 | 1.23E−04 | 0.82 | 0.32 | 1.00E−01 | 0.86 | ||||||||||||
| 12q13.13 | rs3741442 | 53346750 | G/A | 0.46 | 0.41 | 1.17E−06 | 1.22 | 3.72E−12 | 1.22 | 0.44 | 0.42 | 6.42E−02 | 1.10 | 0.99 | 1.00 | 5.42E−01 | 0.72 | 0.54 | 1.30E−04 | 0.77 | 0.41 | 0.98 |
| 0.46 | 0.41 | 3.36E−06 | 1.23 | 0.44 | 0.42 | 9.72E−02 | 1.09 | 0.02 | 2.52E−02 | 0.48 | ||||||||||||
| 12q13.2 | rs705704 | 56435412 | A/G | 0.27 | 0.23 | 4.39E−05 | 1.22 | 1.29E−09 | 1.22 | 0.24 | 0.25 | 2.84E−01 | 0.94 | 0.34 | 0.31 | 7.44E−02 | 1.16 | 0.23 | 6.61E−01 | 1.04 | 0.24 | 0.33 |
| 0.28 | 0.24 | 5.97E−05 | 1.22 | 0.25 | 0.25 | 1.00E+00 | 1.00 | 0.35 | 1.15E−03 | 1.32 | ||||||||||||
| 12q21.1 | rs2304269 | 72080272 | G/A | 0.38 | 0.44 | 1.07E−07 | 0.79 | 1.32E−12 | 0.81 | 0.41 | 0.44 | 2.04E−02 | 0.89 | 0.05 | 0.05 | 7.81E−01 | 0.95 | 0.43 | 2.66E−02 | 0.85 | 0.55 | 0.06 |
| 0.41 | 0.45 | 1.12E−04 | 0.84 | 0.45 | 0.44 | 3.03E−01 | 1.05 | 0.07 | 6.17E−01 | 0.92 | ||||||||||||
| 12q21.1 | rs7967428 | 72089040 | G/A | 0.38 | 0.44 | 1.63E−07 | 0.79 | 3.08E−12 | 0.81 | 0.41 | 0.44 | 6.56E−02 | 0.91 | 0.05 | 0.05 | 9.91E−01 | 1.00 | 0.43 | 2.32E−02 | 0.85 | 0.55 | 0.06 |
| 0.41 | 0.45 | 1.57E−04 | 0.84 | 0.45 | 0.44 | 1.72E−01 | 1.07 | 0.07 | 6.78E−01 | 0.93 | ||||||||||||
| 14q22.1 | rs7148069 | 51839645 | A/G | 0.23 | 0.19 | 1.94E−05 | 1.27 | 1.69E−08 | 1.22 | 0.21 | 0.20 | 6.21E−01 | 1.03 | 0.32 | 0.33 | 7.92E−01 | 0.98 | 0.17 | 8.75E−01 | 1.02 | 0.19 | 0.33 |
| 0.22 | 0.20 | 7.21E−03 | 1.16 | 0.19 | 0.20 | 4.90E−01 | 0.96 | 0.31 | 3.06E−01 | 1.11 | ||||||||||||
| 14q32.13 | rs1243572 | 95379499 | G/A | 0.48 | 0.42 | 1.37E−07 | 1.26 | 3.52E−10 | 1.20 | 0.47 | 0.43 | 7.75E−04 | 1.18 | 0.79 | 0.78 | 3.65E−01 | 1.09 | 0.57 | 7.84E−01 | 0.98 | 0.40 | 0.79 |
| 0.45 | 0.42 | 6.09E−03 | 1.13 | 0.44 | 0.43 | 2.14E−01 | 1.06 | 0.23 | 4.99E−01 | 0.94 | ||||||||||||
| 14q32.13 | rs1243573 | 95379583 | C/A | 0.48 | 0.42 | 2.83E−07 | 1.25 | 8.61E−10 | 1.20 | 0.46 | 0.43 | 8.19E−03 | 1.14 | 0.80 | 0.78 | 4.10E−01 | 1.09 | 0.57 | 7.84E−01 | 0.98 | 0.40 | 0.79 |
| 0.45 | 0.42 | 7.30E−03 | 1.13 | 0.45 | 0.43 | 8.60E−02 | 1.09 | 0.23 | 4.99E−01 | 0.94 | ||||||||||||
| 17q21.32 | rs4968247 | 44988703 | A/G | 0.37 | 0.41 | 4.11E−06 | 0.84 | 8.70E−10 | 0.83 | 0.37 | 0.40 | 1.44E−03 | 0.85 | 0.66 | 0.67 | 4.81E−01 | 0.94 | 0.61 | 2.52E−03 | 1.26 | 0.43 | 0.65 |
| 0.37 | 0.41 | 2.43E−05 | 0.83 | 0.40 | 0.40 | 4.34E−01 | 0.96 | 0.33 | 1.21E−01 | 1.15 | ||||||||||||
| 17q21.32 | rs1838105 | 45008935 | A/G | 0.45 | 0.39 | 1.84E−07 | 1.26 | 1.31E−11 | 1.22 | 0.43 | 0.38 | 5.98E−04 | 1.19 | 0.39 | 0.33 | 5.83E−03 | 1.27 | 0.40 | 1.43E−02 | 1.19 | 0.38 | 0.37 |
| 0.42 | 0.38 | 3.48E−04 | 1.17 | 0.38 | 0.38 | 9.30E−01 | 1.00 | 0.38 | 1.37E−01 | 1.13 | ||||||||||||
F_A, allele frequency in cases; F_U, allele frequency in controls; GWAS. Genome-wide association study; NSCLO, non-syndromic cleft lip only; NSCLP, non-syndromic cleft lip with palate; NSCPO, non-syndromic cleft palate only; SNP, single-nucleotide polymorphism.
NSCLP GWAS: study in 2,033 NSCLP cases and 4,051 controls of Chinese Han (the P-value using logistic regression test); NSCLP replication: replication study in 1,346 NSCLP cases and 4,542 controls of Chinese Han (the P-value using logistic regression test); NSCLP Meta: Meta analysis of NSCLP GWAS and NSCLP replication using fixed model (the P-value using Cochran–Mantel–Haenszel test); NSCLO replication: replication study in 1,104 NSCLO cases and 3,312 controls of Chinese Han (the P-value using logistic regression test); NSCPO replication: replication study in 1,104 NSCPO cases and 3,312 controls shared with NSCLO replication of Chinese Han (the P-value using logistic regression test); NSCL/P replication 1: replication study in 399 NSCL/P cases and 1,318 controls of Central Europeans (the P-value using logistic regression test); NSCL/P replication 2: replication study in 861 NSCL/P case-parent trios of Asian ancestry (the P-value using logistic regression test); NSCL/P replication 3: replication study in 557 NSCL/P case–parent trios of European American ancestry (the P-value using logistic regression test).
*Alleles: shown as minor allele/major allele in Chinese Han samples. Bold denotes entries that reached the thresholds of significance.