Common variants in DLG1 locus are associated with non-syndromic cleft lip with or without cleft palate
Common variants in DLG1 locus are associated with non-syndromic cleft lip with or without cleft palate
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DOI：
10.1111/cge.13141
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发表时间：
2018-04-01
影响因子：
3.5
通讯作者：
Jagodzinski, P. P.
中科院分区：
文献类型：
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作者：
Mostowska, A.;Gaczkowska, A.;Jagodzinski, P. P.
非综合征性唇裂伴或不伴腭裂（nsCL/P）是一种常见的颅面畸形，病因复杂且多样。关于这种出生缺陷背后的特定遗传因素，人们的了解仍然不足。因此，我们对位于3号染色体3q29区域的DLG1基因座内的首要相关变异进行了独立的重复分析，该基因座在我们的全基因组关联研究（GWAS）中被确定为一个新的腭裂易感性位点。对来自GWAS和重复研究的合并个体数据进行的大型分析证实，常见的DLG1变异与nsCL/P的风险相关。两个单核苷酸多态性（SNP），rs338217和rs7649443，甚至在全基因组水平上都具有统计学意义（P趋势分别为9.70×10⁻¹⁰和8.96×10⁻⁹）。另外三个SNP，rs9826379、rs6805920和rs6583202，达到了提示性的全基因组显著性阈值（P趋势……（此处原文未完整给出P趋势相关完整内容）
Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a common craniofacial anomaly with a complex and heterogeneous aetiology. Knowledge regarding specific genetic factors underlying this birth defect is still not well understood. Therefore, we conducted an independent replication analysis for the top-associated variants located within the DLG1 locus at chromosome 3q29, which was identified as a novel cleft-susceptibility locus in our genome-wide association study (GWAS). Mega-analysis of the pooled individual data from the GWAS and replication study confirmed that common DLG1 variants are associated with the risk of nsCL/P. Two single nucleotide polymorphisms (SNPs), rs338217 and rs7649443, were statistically significant even at the genome-wide level (P-trend=9.70E-10 and P-trend=8.96E-09, respectively). Three other SNPs, rs9826379, rs6805920 and rs6583202, reached a suggestive genome-wide significance threshold (P-trend