Validation of a genome-wide association study implied that SHTIN1 may involve in the pathogenesis of NSCL/P in Chinese population.

Yirui Wang,Jing Cheng,Lan Ma,Lei Zhang,Yimin Sun,Lin Wang,Jiayu Shi,Hongbing Jiang,Xue Xiao,Yongqing Huang,Xuefei Du,Yinxue Yang,Min Jiang,Zhongwei Zhou,Bing Shi,Yongchu Pan,Aihua Yin,Feifei Lan

doi:10.1038/srep38872

Abstract

Orofacial clefts are among the most common birth defects in humans worldwide. A large-scale, genome-wide association study (GWAS) in the Chinese population recently identified several genetic risk variants for nonsyndromic cleft lip with or without cleft palate (NSCL/P). We selected 16 significant SNPs from the GWAS I stage (P < 1.00E-5) that had not been replicated to validate their association with NSCL/P in 1931 NSCL/P cases and 2258 controls. Ultimately, we identified a NSCL/P susceptibility loci (rs17095681 at 10q25.3, intron of SHTN1 and 27.2 kb downstream of VAX1, Pmeta = 3.80E-9, OR = 0.64) in Chinese Han and Hui populations. This locus was not high LD with the reported loci in 10q25.3. It was a newly identified independent locus in 10q25.3 associated with NSCL/P. These results imply that SHTIN1 may involve in the pathogenesis of NSCL/P advance our understanding of the genetic susceptibility to NSCL/P.

Highlights

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common birth defects with heterogeneous etiologies, including both genetic and environmental factors and their joint effects[1]
P-value of the genome-wide association studies (GWAS) and validation stage. In this validation study of NSCL/P, we identified one single nucleotide polymorphism (SNP) at 10q25.3, rs17095681, which were significantly associated with NSCL/P risk in Chinese Han and Hui populations
The SNP rs17095681 is located in the intron of SHTN1 and 27.2 kb downstream of VAX1

Summary

Introduction

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common birth defects with heterogeneous etiologies, including both genetic and environmental factors and their joint effects[1]. We selected 16 such SNPs and validated them in Chinese population to further identify susceptibility loci/genes for NSCL/P. We performed the validation of these 16 SNPs in 1668 Chinese Han cases and 1924 Chinese Han controls from multiple hospitals in China.

Results

Conclusion