rs987525

A targeted genome-wide study examining SNPs in three understudied populations (260 children with orofacial clefts from the DRC, Vietnam, and Philippines) confirmed four cleft susceptibility regions: 1q32.2 (IRF6), 10q25.3 (VAX1), 17q22 (NOG), and 15q13.3. Notable findings include rs10787738 near VAX1 (P=4.98E-03) and rs7987165 on chromosome 13 (P=2.2E-05) in meta-analysis, with risk alleles varying by population and no significant associations found in African populations.

This replication study investigated common and rare variants in PAX7 and VAX1 genes associated with non-syndromic cleft lip with or without palate (CL(P)). Using TDT analysis in case-parent triads and family-based sequencing of 1,326 individuals from four populations, the study confirmed strong associations with VAX1 markers rs7078160 (p=7.4E-09 in combined samples) and rs4752028 (p=9.8E-06), replicated previous GWAS findings in Asian populations, and identified eight rare missense mutations in PAX7 and two in VAX1 that may contribute to CL(P) etiology.

This Brazilian population study examines IRF6 gene variants rs642961 and rs590223 for association with nonsyndromic cleft lip/palate (NSCL/P) in 471 patients and 391 controls. A significant association was found between rs642961 and cleft lip only (CLO, P=0.009; OR 1.72-1.83), with a dominant genetic model, particularly in the high-heritability Barbalha subpopulation. No association was detected for rs590223, and expression analysis in mesenchymal stem cells showed no correlation between SNP genotypes and IRF6 expression levels.

This case-control study of 396 nonsyndromic orofacial cleft cases and 384 controls in a Chinese Han population confirms that rs13041247 near MAFB is associated with decreased NSOC risk (C allele frequency 0.497 in controls vs 0.356 in cases), with protective effects observed across cleft lip phenotypes. The rs560426 variant near ABCA4 showed no significant association with NSOC in this population, demonstrating population-specific effects of previously identified GWAS loci.

A large candidate gene study testing associations between nonsyndromic oral clefts and 12 genes (CLPTM1, CRISPLD2, FGFR2, GABRB3, GLI2, IRF6, PTCH1, RARA, RYK, SATB2, SUMO1, TGFA) in an Irish population of 509 cleft lip with or without palate (CLP) cases, 383 cleft palate only cases, and 902 controls. The study confirmed associations with PTCH1, SUMO1, and TGFA as contributing to nonsyndromic oral clefts, with PTCH1 P1315L showing significant association with CLP.

Family-based study of 120 multiplex families and 325 simplex trios confirming association between six SNPs on chromosome 8q24.21 and nonsyndromic cleft lip and palate (NSCLP) in non-Hispanic whites, with relative risks ranging from 1.01-1.55 for heterozygotes and homozygotes. The study demonstrates ethnic heterogeneity, finding no association in Hispanic families and no linkage in African-American families, suggesting the 8q24 locus affects primarily individuals of Western European descent.