Integrating GWAS and eQTL to predict genes and pathways for non-syndromic cleft lip with or without palate
Integrating GWAS and eQTL to predict genes and pathways for non-syndromic cleft lip with or without palate
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DOI：
10.1111/odi.13699
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发表时间：
2020-12-14
期刊：
影响因子：
3.8
通讯作者：
Pan，Yongchu
中科院分区：
文献类型：
--
作者：
Yang，Jing;Yu，Xin;Pan，Yongchu
目的探讨非综合征型唇裂伴或不伴腭裂（NSCL/P）的易感基因和易感途径。材料和方法将858例NSCL/P病例和1248例对照组的2个全基因组关联研究（GWAS）数据集与基因型-组织表达（GTEx）项目在全血样本中鉴定的表达数量性状位点（eQTL）数据集进行整合。通过FaceBase查询候选基因在小鼠口面部发育中的表达情况。蛋白质-蛋白质相互作用（PPI）网络可视化，以确定蛋白质的功能。进行Go和KEGG通路分析以探索潜在的风险通路。结果共鉴定出432个候选基因中233个eQTL单核苷酸多态性（snp）与nsl /P风险相关。根据FaceBase， 183个易感基因在小鼠口腔面部发育中表达。PPI网络分析强调，这些参与泛素介导的蛋白水解（KCTD7、ASB1、UBOX5、ANAPC4）和DNA合成（XRCC3、RFC3、KAT5、RHNO1）的基因与nsl /P的风险相关。GO和KEGG通路分析显示脂肪酸代谢通路（ACADL、HSD17B12、ACSL5、PPT1、MCAT）在NSCL/P的发生发展中发挥重要作用。结论sour结果发现了与nsl /P发生发展相关的新的易感基因和通路。
ObjectiveTo explore susceptibility genes and pathways for non‐syndromic cleft lip with or without cleft palate (NSCL/P).Materials and methodsTwo genome‐wide association studies (GWAS) datasets, including 858 NSCL/P cases and 1,248 controls, were integrated with expression quantitative trait loci (eQTL) dataset identified by Genotype‐Tissue Expression (GTEx) project in whole‐blood samples. The expression of the candidate genes in mouse orofacial development was inquired from FaceBase. Protein–protein interaction (PPI) network was visualized to identify protein functions. Go and KEGG pathway analyses were performed to explore the underlying risk pathways.ResultsA total of 233 eQTL single‐nucleotide polymorphisms (SNPs) in 432 candidate genes were identified to be associated with the risk of NSCL/P. One hundred and eighty‐three susceptible genes were expressed in mouse orofacial development according to FaceBase. PPI network analysis highlighted that these genes involved in ubiquitin‐mediated proteolysis (KCTD7,ASB1,UBOX5,ANAPC4) and DNA synthesis (XRCC3,RFC3,KAT5,RHNO1) were associated with the risk of NSCL/P. GO and KEGG pathway analyses revealed that the fatty acid metabolism pathway (ACADL,HSD17B12,ACSL5,PPT1,MCAT) played an important role in the development of NSCL/P.ConclusionsOur results identified novel susceptibility genes and pathways associated with the development of NSCL/P.