Table 2.
Part A: Meta-analyses of NSCL/P and NSCPO Case-Control Cohorts from All 3 Countries | |||||||||
---|---|---|---|---|---|---|---|---|---|
NSCL/P |
NSCPO |
||||||||
SNP | Probable Gene/Loci | Minor Allelesa | African MAF | P | OR | I | P | OR | I |
rs1801131 | MTHFR | C/Ab | 0.15 | 0.32 | 1.08 | 0.00 | 0.19 | 0.79 | 0.00 |
rs1801133 | MTHFR | A/Gc | 0.09 | 0.49 | 1.08 | 18.19 | 0.44 | 0.83 | 0.00 |
rs766325 | PAX7 | G/Ab,d,e | 0.18 | 0.29 | 0.92 | 0.00 | 0.23 | 0.82 | 0.00 |
rs742071 | PAX7 | T/Gb | 0.39 | 5.10E-03f | 1.19 | 54.68 | 0.76 | 0.96 | 0.00 |
rs560426 | ABCA4 | C/Tb,g | 0.49 | 0.10 | 0.90 | 6.15 | 0.16 | 1.18 | 0.00 |
rs481931 | ABCA4 | T/Gc | 0.10 | 0.40 | 1.09 | 11.13 | 0.49 | 0.85 | 0.00 |
rs4147811 | ABCA4 | T/Cc | 0.11 | 0.23 | 1.13 | 67.35 | 0.93 | 1.02 | 0.00 |
rs138751793 | ARHGAP29 | C/Th | 0.02 | 0.24 | 1.32 | 0.00 | 0.47 | 1.34 | 27.90 |
rs6677101 | SLC25A24 | G/Tb,e,g | 0.33 | 0.80 | 0.98 | 12.11 | 0.87 | 1.02 | 53.89 |
rs861020 | IRF6 | A/Gb | 0.11 | 0.23 | 1.11 | 0.00 | 0.83 | 0.96 | 24.15 |
rs34743335 | IRF6 | T/A | 0.02 | 0.59 | 0.90 | 0.00 | 0.84 | 0.89 | 38.34 |
rs642961 | IRF6 | A/Gb | 0.09 | 0.32 | 1.11 | 68.47 | 0.57 | 0.88 | 44.17 |
rs7590268 | THADA | G/Tb | 0.20 | 0.74 | 0.98 | 0.00 | 0.38 | 0.87 | 0.00 |
rs4332945 | DYSF | T/Gb,e,g | 0.16 | 0.94 | 0.99 | 0.00 | 0.97 | 1.01 | 0.00 |
rs2303596 | DYSF | T/Cc,d,e | 0.22 | 0.20 | 0.91 | 75.32 | 0.57 | 1.09 | 73.54 |
rs227782 | DYSF | A/Gb,g | 0.42 | 0.33 | 1.06 | 0.00 | 0.35 | 1.12 | 61.90 |
rs115200552 | MSX1 | C/Gh | 0.02 | 0.38 | 1.16 | 28.63 | 0.01f | 1.81 | 0.00 |
rs12532 | MSX1 | G/Ac,e | 0.44 | 0.49 | 0.96 | 0.00 | 0.37 | 0.90 | 0.43 |
rs2674394 | Gene desert | A/Cb | 0.17 | 0.62 | 1.04 | 0.00 | 0.68 | 1.07 | 0.00 |
rs651333 | TULP4 | C/Tb,d,g | 0.34 | 0.97 | 1.00 | 0.00 | 0.04f | 1.29 | 0.00 |
rs6558002 | EPHX2 | C/Tb,g | 0.24 | 0.39 | 1.06 | 0.00 | 0.87 | 1.02 | 0.00 |
rs987525 | 8q24 | A/Cb,g | 0.38 | 1.22E-03f | 0.81 | 40.55 | 0.22 | 0.86 | 0.00 |
rs894673 | FOXE1 | A/Tc | 0.33 | 0.42 | 0.95 | 0.00 | 0.93 | 1.01 | 0.00 |
rs3758249 | FOXE1 | T/Cc | 0.33 | 0.56 | 0.96 | 0.00 | 0.90 | 1.02 | 0.00 |
rs7078160 | VAX1 | A/Gb | 0.25 | 0.04f | 1.16 | 0.00 | 0.88 | 1.02 | 0.00 |
rs4752028 | VAX1 | C/Tb,g | 0.45 | 0.51 | 0.96 | 0.00 | 0.80 | 0.97 | 0.00 |
rs10785430 | ADAMTS20 | G/Ab | 0.32 | 0.90 | 0.99 | 0.00 | 0.49 | 1.09 | 0.00 |
rs9574565 | SPRY2 | T/Cc,g | 0.35 | 0.75 | 1.02 | 0.00 | 0.45 | 1.10 | 0.00 |
rs8001641 | SPRY2 | G/Ac,d,e,g | 0.10 | 0.35 | 1.08 | 0.00 | 0.37 | 0.85 | 0.00 |
rs17563 | BMP4 | T/Cb,d,e,g | 0.18 | 0.95 | 0.99 | 0.00 | 0.77 | 1.04 | 0.00 |
rs1258763 | GREM1 | C/Tc,d,e,g | 0.49 | 0.11 | 1.11 | 0.00 | 0.50 | 0.92 | 0.00 |
rs8049367 | ADCY9 | C/Tc,d,e | 0.30 | 0.20 | 1.09 | 0.00 | 0.10 | 0.81 | 0.00 |
rs16260 | CDH1 | A/Cb | 0.13 | 0.59 | 1.05 | 0.00 | 0.39 | 0.85 | 0.00 |
rs11642413 | CDH1 | G/Ab,e,g | 0.28 | 0.83 | 1.02 | 0.00 | 0.21 | 0.83 | 0.00 |
rs1546124 | CRISPLD2 | G/Cb,e | 0.25 | 0.60 | 0.96 | 0.00 | 0.89 | 0.98 | 0.00 |
rs4783099 | CRISPLD2 | T/Cb | 0.33 | 0.59 | 1.04 | 0.00 | 0.02f | 0.74 | 0.00 |
rs8069536 | NTN1 | T/Gb | 0.32 | 0.13 | 1.11 | 0.97 | 0.88 | 0.98 | 0.00 |
rs8081823 | NTN1 | A/Gc | 0.24 | 0.08 | 0.88 | 0.00 | 0.63 | 0.94 | 32.54 |
rs17760296 | NOG1 | G/Tb | 0.02 | 0.92 | 0.99 | 0.00 | 0.04f | 1.74 | 0.00 |
rs227731 | NOG1 | G/Tb,g | 0.22 | 0.86 | 0.99 | 0.00 | 0.26 | 1.17 | 0.00 |
rs7224837 | AXIN2 | G/Ab | 0.11 | 0.75 | 1.04 | 0.00 | 0.81 | 0.95 | 0.00 |
rs3923086 | AXIN2 | A/Cb,d,e,g | 0.02 | 0.25 | 1.15 | 0.00 | NA | NA | NA |
rs17820943 | MAFB | T/Cc | 0.25 | 0.33 | 0.93 | 15.15 | 0.68 | 1.06 | 22.99 |
rs13041247 | MAFB | C/Tc | 0.25 | 0.37 | 0.94 | 34.01 | 0.42 | 1.12 | 0.00 |
rs11696257 | MAFB | T/Cc | 0.25 | 0.30 | 0.93 | 32.24 | 0.61 | 1.07 | 0.00 |
Part B: Meta-analyses of Subphenotypes of NSCL/P Cohorts from the 3 Countries | |||||||||
NSCL |
NSCLP |
||||||||
rs1801131 | MTHFR | C/Ab | 0.15 | 0.78 | 1.03 | 0.00 | 0.22 | 1.13 | 0.00 |
rs1801133 | MTHFR | A/Gc | 0.09 | 0.71 | 1.06 | 8.24 | 0.30 | 0.30 | 0.00 |
rs766325 | PAX7 | G/Ab,d,e | 0.18 | 0.91 | 0.99 | 0.00 | 0.17 | 0.86 | 0.00 |
rs742071 | PAX7 | T/Gb | 0.39 | 0.02f | 1.23 | 68.74 | 0.03f | 1.19 | 0.00 |
rs560426 | ABCA4 | C/Tb | 0.49 | 0.73 | 1.03 | 0.00 | 0.03f | 1.20 | 10.33 |
rs481931 | ABCA4 | T/Gc | 0.10 | 0.81 | 0.97 | 0.00 | 0.08 | 1.27 | 63.75 |
rs4147811 | ABCA4 | T/Cc | 0.11 | 0.50 | 1.10 | 65.82 | 0.15 | 1.21 | 15.35 |
rs138751793 | ARHGAP29 | C/Th | 0.02 | 0.19 | 1.53 | 66.38 | 0.41 | 1.29 | 0.00 |
rs6677101 | SLC25A24 | G/Tb,e,g | 0.33 | 0.92 | 0.99 | 0.00 | 0.98 | 1.00 | 58.97 |
rs861020 | IRF6 | A/Gb | 0.11 | 0.18 | 1.17 | 17.72 | 0.57 | 1.07 | 0.00 |
rs34743335 | IRF6 | T/A | 0.02 | 0.87 | 0.96 | 0.00 | 0.50 | 0.85 | 23.72 |
rs642961 | IRF6 | A/Gb | 0.09 | 0.96 | 0.99 | 15.60 | 0.15 | 1.21 | 62.97 |
rs7590268 | THADA | G/Tb | 0.20 | 0.45 | 0.92 | 0.00 | 0.50 | 1.07 | 0.00 |
rs4332945 | DYSF | T/Gb,e,g | 0.16 | 0.54 | 0.94 | 10.40 | 0.71 | 1.04 | 0.00 |
rs2303596 | DYSF | T/Cc,d,e | 0.22 | 0.29 | 0.89 | 63.58 | 0.44 | 0.93 | 75.54 |
rs227782 | DYSF | A/Gb,g | 0.42 | 0.85 | 0.98 | 0.00 | 0.13 | 1.14 | 0.00 |
rs115200552 | MSX1 | C/Gh | 0.02 | 0.18 | 1.37 | 61.30 | 0.68 | 1.10 | 0.00 |
rs12532 | MSX1 | G/Ac,e | 0.44 | 0.55 | 0.95 | 0.00 | 0.51 | 0.95 | 0.00 |
rs2674394 | Gene desert | A/Cb | 0.17 | 0.06 | 1.22 | 0.00 | 0.42 | 0.91 | 0.00 |
rs651333 | TULP4 | C/Tb,d,g | 0.34 | 0.63 | 0.96 | 0.00 | 0.74 | 0.97 | 0.00 |
rs6558002 | EPHX2 | C/Tb,g | 0.24 | 0.82 | 1.02 | 0.00 | 0.11 | 0.11 | 0.00 |
rs987525 | 8q24 | A/Cb,g | 0.38 | 5.38E-03f | 1.28 | 0.00 | 0.01f | 0.80 | 54.21 |
rs894673 | FOXE1 | A/Tc | 0.33 | 0.54 | 0.95 | 42.39 | 0.45 | 0.94 | 0.00 |
rs3758249 | FOXE1 | T/Cc | 0.33 | 0.53 | 0.94 | 46.73 | 0.68 | 0.96 | 0.00 |
rs7078160 | VAX1 | A/Gb | 0.25 | 0.03f | 1.23 | 0.00 | 0.20 | 1.13 | 24.04 |
rs4752028 | VAX1 | C/Tb,g | 0.45 | 0.55 | 1.05 | 16.64 | 0.50 | 0.95 | 0.00 |
rs10785430 | ADAMTS20 | G/Ab | 0.32 | 0.88 | 1.01 | 41.30 | 0.86 | 0.98 | 3.00 |
rs9574565 | SPRY2 | T/Cc,g | 0.35 | 0.53 | 1.06 | 72.62 | 0.43 | 1.07 | 65.44 |
rs8001641 | SPRY2 | G/Ac,d,e,g | 0.10 | 0.99 | 1.00 | 0.00 | 0.26 | 1.13 | 0.00 |
rs17563 | BMP4 | A/Gb,d,e,g | 0.18 | 0.89 | 0.99 | 25.84 | 0.98 | 1.00 | 0.00 |
rs1258763 | GREM1 | C/Tc,d,e,g | 0.49 | 0.22 | 0.90 | 0.00 | 0.10 | 1.15 | 0.00 |
rs8049367 | ADCY9 | C/Tc,d,e | 0.30 | 0.36 | 1.09 | 10.19 | 0.35 | 1.08 | 0.00 |
rs16260 | CDH1 | A/Cb | 0.13 | 0.46 | 0.91 | 10.51 | 0.20 | 1.16 | 0.00 |
rs11642413 | CDH1 | G/Ab,e,g | 0.28 | 0.98 | 1.00 | 0.00 | 0.55 | 1.05 | 0.00 |
rs1546124 | CRISPLD2 | G/Cb,e | 0.25 | 0.26 | 0.90 | 0.00 | 0.88 | 1.01 | 0.00 |
rs4783099 | CRISPLD2 | T/Cb | 0.33 | 0.85 | 1.02 | 0.00 | 0.32 | 1.09 | 0.00 |
rs8069536 | NTN1 | T/Gb | 0.32 | 0.72 | 1.03 | 3.47 | 0.04f | 1.20 | 0.00 |
rs8081823 | NTN1 | A/Gc | 0.24 | 0.55 | 0.95 | 0.00 | 0.05 | 0.83 | 0.00 |
rs17760296 | NOG1 | G/Tb | 0.02 | 0.83 | 1.04 | 5.85 | 0.85 | 0.97 | 0.00 |
rs227731 | NOG1 | G/Tb,g | 0.22 | 0.38 | 0.92 | 0.00 | 0.59 | 1.05 | 0.00 |
rs7224837 | AXIN2 | G/Ab | 0.11 | 0.61 | 1.08 | 0.00 | 0.81 | 1.04 | 0.00 |
rs3923086 | AXIN2 | A/Cb,d,e,g | 0.02 | 0.62 | 1.10 | 40.28 | NA | NA | 0.00 |
rs17820943 | MAFB | T/Cc | 0.25 | 0.25 | 0.89 | 15.55 | 0.43 | 0.93 | 0.00 |
rs13041247 | MAFB | C/Tc | 0.25 | 0.25 | 0.89 | 31.03 | 0.54 | 0.94 | 0.00 |
rs11696257 | MAFB | T/Cc | 0.25 | 0.24 | 0.89 | 27.17 | 0.40 | 0.92 | 0.00 |
All P values reported are for the minor alleles. All initial studies were carried out in Asians and/or Caucasians but not Africans. Source of minor alleles and MAF: http://browser.1000genomes.org.
I, test of heterogeneity of which 0 to 40 represents no heterogeneity; MAF, minor allele frequency; NA, not applicable; NSCL, nonsyndromic cleft lip; NSCL/P, nonsyndromic cleft lip with or without cleft palate; NSCLP, nonsyndromic cleft lip and palate; NSCPO, nonsyndromic cleft palate only; OR, odds ratio; SNP, single-nucleotide polymorphism.
The first allele is the minor allele in Europeans unless otherwise indicated. The first allele is also the minor allele in East Asians, South Asians, and Africans.
Minor allele was the risk allele in initial study.
Minor allele was protective in initial study.
The first allele is the major allele, while the second allele is the minor allele in South Asians.
The first allele is the major allele, while the second allele is the minor allele in East Asians.
Loci that reached nominal significance in meta-analyses (in bold).
The first allele is the major allele, while the second allele is the minor allele in Africans.
The first allele is the minor allele, and the variation exists only in Africans.