1] Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, China [2] The State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China [3] CapitalBio Corporation, Beijing 102206, China [4] National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, China.
1] General Hospital of Ningxia Medical University, Yinchuan 750004, China [2] National Engineering Research Center for Beijing Biochip Technology, Sub-center in Ningxia, Yinchuan 750004, China.
Nat Commun. 2015 Mar 16;6:6414. doi: 10.1038/ncomms7414.
Nonsyndromic cleft lip with or without a cleft palate (NSCL/P) is among the most common human congenital birth defects and imposes a substantial physical and financial burden on affected individuals. Here, we conduct a case-control-based GWAS followed by two rounds of replication; we include six independent cohorts from China to elucidate the genetic architecture of NSCL/P in Chinese populations. Using this combined analysis, we identify a new locus at 16p13.3 associated with NSCL/P: rs8049367 between CREBBP and ADCY9 (odds ratio=0.74, P=8.98 × 10(-12)). We confirm that the reported loci at 1q32.2, 10q25.3, 17p13.1 and 20q12 are also involved in NSCL/P development in Chinese populations. Our results provide additional evidence that the rs2235371-related haplotype at 1q32.2 could play a more important role than the previously identified causal variant rs642961 in Chinese populations. These findings provide information on the genetic basis and mechanisms of NSCL/P.
非综合征性唇裂伴或不伴腭裂（NSCL/P）是最常见的人类先天性出生缺陷之一，给患者个人带来了巨大的身体和经济负担。在这里，我们进行了一项基于病例对照的 GWAS 研究，并进行了两轮复制；我们纳入了来自中国的六个独立队列，以阐明中国人群中 NSCL/P 的遗传结构。通过这项综合分析，我们在 16p13.3 发现了一个与 NSCL/P 相关的新位点：位于 CREBBP 和 ADCY9 之间的 rs8049367（比值比=0.74，P=8.98×10(-12)）。我们证实，先前报道的 1q32.2、10q25.3、17p13.1 和 20q12 位点也与中国人群中 NSCL/P 的发生有关。我们的研究结果提供了额外的证据，表明 1q32.2 上与 rs2235371 相关的单倍型可能比先前在中国人中鉴定到的因果变异 rs642961 发挥更重要的作用。这些发现为 NSCL/P 的遗传基础和机制提供了信息。
