Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, China.
CapitalBio Corporation, Beijing 102206, China.
Sci Rep. 2016 Dec 23;6:38872. doi: 10.1038/srep38872.
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, P = 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.
口腔颌面部裂是全球最常见的出生缺陷之一。最近，一项针对中国人的大规模全基因组关联研究（GWAS）确定了几个非综合征性唇裂伴或不伴腭裂（NSCL/P）的遗传风险变异。我们从 GWAS I 阶段（P < 1.00E-5）中选择了 16 个未被复制的显著 SNP，以验证它们与 1931 例 NSCL/P 病例和 2258 例对照的关联。最终，我们在中国汉族和回族人群中确定了一个 NSCL/P 易感位点（10q25.3 上的 rs17095681，位于 SHTN1 的内含子和 VAX1 的下游 27.2kb 处，P = 3.80E-9，OR = 0.64）。该位点与 10q25.3 上报道的位点无高度连锁。这是 10q25.3 中与 NSCL/P 相关的一个新的独立位点。这些结果表明 SHTIN1 可能参与了 NSCL/P 的发病机制，进一步加深了我们对 NSCL/P 遗传易感性的理解。
