rs7078160

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.

A systematic review and meta-analysis of 7 case-control studies (3,002 total participants: 1,483 cases and 1,519 controls) examined the association between VAX1 polymorphisms rs7078160 and rs4752028 with non-syndromic cleft lip with or without cleft palate (NSCL/P). For rs7078160, the AA genotype conferred increased NSCL/P risk (OR = 2.34, 95% CI: 1.55-3.24) compared with GG, and AG carriers also showed increased risk (OR = 1.31, 95% CI: 1.11-1.54). For rs4752028, CC carriers showed increased risk (OR = 1.47, 95% CI: 1.09-1.97) and CT carriers (OR = 1.28, 95% CI: 1.01-1.52). Associations were stronger in non-Chinese populations with evidence of publication bias for rs4752028.

A systematic review and meta-analysis of 7 case-control studies (1,483 cases and 1,519 controls) evaluated the association of VAX1 polymorphisms rs7078160 and rs4752028 with non-syndromic cleft lip with or without cleft palate (NSCL/P). For rs7078160, the AA genotype showed significantly increased NSCL/P risk versus GG (OR = 2.34, 95% CI: 1.55-3.24), and AG carriers also showed increased risk (OR = 1.31, 95% CI: 1.11-1.54). For rs4752028, CC versus TT showed OR = 1.47 (95% CI: 1.09-1.97), and CT versus TT showed OR = 1.28 (95% CI: 1.01-1.52). Stronger associations were observed in non-Chinese populations, though publication bias was detected for rs4752028.

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.