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. 2022 Jan 24;12:1214. doi: 10.1038/s41598-021-02159-5

Table 2.

Results of the meta-analysis performed to determine the associations between the genetic markers and the different non-syndromic orofacial cleft phenotypes in populations of European ancestry; results for the genes where there were significant associations with moderate effect sizes.

Gene Varianta A/a Phenotype N NCA NCO Allelic modelb Dominant modelc Recessive modeld Overdominant modele
OR (95% CI) p-value OR (95% CI) p-value OR (95% CI) p-value OR (95% CI) p-value
ABCA4 rs560426 G/A CL/P 2 582 846 1.16 (0.70–1.94) 0.570 1.14 (0.66–1.97) 0.642 1.31 (0.58–2.96) 0.523 0.89 (0.72–1.11) 0.298
rs481931** C/A CL/P 2 589 849 0.78 (0.67–0.91) 0.002 0.74 (0.60–0.92) 0.008 0.70 (0.52–0.96) 0.025# 0.92 (0.60–1.41) 0.709
WNT3a rs708111** T/C OFC 2 673 547 1.16 (0.99–1.37) 0.068 NA NA NA NA NA NA
CL/P 2 582 547 1.20 (1.02–1.42) 0.032# NA NA NA NA NA NA
rs752107 C/T OFC 2 673 547 0.91 (0.76–1.08) 0.290 NA NA NA NA NA NA
CL/P 2 582 547 0.88 (0.74–1.06) 0.170 NA NA NA NA NA NA
WNT5a rs566926** C/A OFC 2 673 547 1.24 (1.04–1.49) 0.020 NA NA NA NA NA NA
CL/P 2 582 547 1.28 (1.06–1.54) 0.010 NA NA NA NA NA NA
FOXE1 rs4460498** C/T OFC 2 1206 1302 0.79 (0.71–0.89) < 0.0001 0.77 (0.55–1.08) 0.131 0.78 (0.62–0.98) 0.034# 0.82 (0.70–0.96) 0.012#
CL/P 2 1060 1302 0.77 (0.68–0.87) < 0.0001 0.76 (0.53–1.11) 0.153 0.73 (0.57–0.93) 0.010# 0.82 (0.70–0.97) 0.019#
rs3758249** G/A OFC 2 1200 1301 0.81 (0.72–0.91) 0.0004 0.85 (0.52–1.40) 0.530 0.79 (0.63–1.00) 0.053 0.97 (0.58–1.61) 0.908
CL/P 2 1055 1302 0.84 (0.65–1.08) 0.168 0.84 (0.50–1.42) 0.524 0.74 (0.58–0.94) 0.016# 0.97 (0.59–1.61) 0.919
GREM1 rs1258763** A/G CL/P 2 435 1203 0.71 (0.60–0.84) < 0.0001 0.60 (0.48–0.75) < 0.00001 0.78 (0.53–1.13) 0.186 0.66 (0.53–0.82) 0.0002
DVL2 rs35594616** C/T OFC 2 705 630 1.14 (0.97–1.33) 0.106 1.46 (1.16–1.83) 0.001 0.78 (0.39–1.55) 0.476 1.58 (1.11–2.23) 0.010
rs2074222** G/A OFC 2 744 615 1.08 (0.92–1.27) 0.331 1.29 (1.03–1.61) 0.026# 0.74 (0.29–1.89) 0.533 1.42 (0.90–2.24) 0.134
rs222836* C/T OFC 2 702 616 1.18 (1.01–1.37) 0.038# 1.38 (0.75–2.53) 0.296 1.15 (0.90–1.47) 0.277 1.13 (0.61–2.11) 0.692
NOG rs227731** A/C OFC 3 471 1020 1.38 (1.18–1.62) < 0.0001 1.59 (1.24–2.03) 0.0002 1.47 (1.13–1.91) 0.004 1.13 (0.91–1.41) 0.269
CL/P 2 306 694 1.33 (1.10–1.61) 0.003 1.63 (1.20–2.23) 0.002 1.25 (0.75–2.06) 0.392 1.23 (0.94–1.61) 0.137
AXIN2 rs2240308** G/A OFC 2 369 513 0.94 (0.77–1.13) 0.505 0.75 (0.55–1.02) 0.067 1.13 (0.82–1.56) 0.452 0.74 (0.56–0.97) 0.027#
CL/P 2 359 513 0.94 (0.77–1.14) 0.525 0.74 (0.54–1.01) 0.057 1.15 (0.83–1.59) 0.392 0.72 (0.55–0.95) 0.020#

A/a, major and minor alleles, where major allele is listed first and risk allele is underlined; Phenotype, non-syndromic orofacial cleft phenotype studied (CL/P, cleft lip with or without cleft palate; CPO, cleft palate only; OFC, all phenotypes combined); N, number of studies included in the analysis (allelic model); NCA, total number of cases included in the analysis (allelic model); NCO, total number of controls included in the analysis (allelic model); NA, not available; OR (95% CI), pooled odds ratio with 95% confidence interval for each analysis.

Abbreviations of gene names are given in Supplementary Table S4 and further details about the meta-analysis are presented in Supplementary Table S6.

*Significant results with moderate (**) and small (*) effect sizes; the largest values for the variant were considered, regardless of the phenotype studied or genetic model used.

#Results that did not remain significant after applying Bonferroni correction.

aGenetic variants found in named genes or in their close proximity; listed based on chromosomal location; bminor allele (a) vs. major allele (A); cAa + aa vs. AA; daa vs. Aa + AA; eAa vs. AA + aa. Statistically significant results are in bold.