NTN1 gene was risk to non-syndromic cleft lip only among Han Chinese population

Genome-wide association studies (GWAS) found NTN1, NOG and the region between CREBBP and ADCY9 were risks to non-syndromic cleft lip with or without cleft palate (NSCL/P). However, the association of single nucleotide polymorphisms (SNPs) in these genes with NSCL/P in Western China is unknown.

We selected seven SNPs in NTN1, NOG and between CREBBP and ADCY9, and then performed transmission disequilibrium test (TDT), parent-of-origin effect and sliding window haplotype analysis to test the associations among 302 NSCL/P case-parent trios from Western Han Chinese.

We found allele G at rs4791774 in NTN1 was significantly overtransmitted among non-syndromic cleft lip only (NSCLO) (p = 0.0067, OR = 1.79, 95% CI: 1.17-2.74); rs4791774 and rs9915089 tightly linked with each other among NSCL/P (D' = 0.87, r²  = 0.67) and haplotypes carrying the risk allele G at rs4791774 were always found to be overtransmitted from parents to cases. Motif analysis indicated that allele G at rs4791774 could greatly alter the affinity of Myc_disc7, so allele G at rs4791774 in NTN1 might modulate C-MYC transcription to participate in the aetiology of NSCLO.

Our study suggested allele G at rs4791774 in NTN1 gene is risk of NSCLO, which could greatly increase the risk to have a baby with cleft.