Targeted Resequencing Identifies Novel MAFB Variants Associated With Nonsyndromic Cleft Lip With or Without Cleft Palate

Objectives Nonsyndromic cleft lip with or without palate (NSCL/P) is one of the most prevalent congenital orofacial defects. It arises from a combination of genetic and environmental factors. This study aims to identify new risk loci around the musculoaponeurotic fibrosarcoma oncogene family, protein B ( MAFB ) gene in NSCL/P patients from the Western Han Chinese population. Design A targeted region sequencing approach was employed to examine the MAFB gene in 159 NSCL/P cases. We conducted both single-variant association and gene-based burden analyses. Setting The study was conducted in a stomatological hospital. Patients, participants One hundred and fifty-nine NSCL/P cases were analyzed. Interventions Blood samples were collected. Main outcome measures To explore the association analysis between variants at MAFB and NSCL/P in Western Han Chinese population. Results We identified a cluster of significant common variants near the 3’ end of MAFB . Notably, rs6029223 showed significantly associated with NSCL/P ( P = 3.82E-09, odds ration [OR] = 0.29, 95% confidence interval [CI]: 0.18–0.46), nonsyndromic cleft lip and palate (NSCLP) ( P = 5.31E-08, OR = 0.25, 95% CI: 0.14–0.44) and nonsyndromic cleft lip only (NSCLO) ( P = 1.3E-04, OR = 0.34, 95%CI: 0.19–0.62). In Addition, rs79836852 and rs200392238 were significantly associated with both NSCL/P and NSCLP. Conclusions Our study revealed that single nucleotide polymorphisms near the 3’ end of the MAFB gene are risk factors for NSCL/P and NSCLP in the Western Han Chinese population. Our findings reinforce the notion that MAFB is a susceptibility gene for NSCL/P.