WNT信号通路基因位点单体型与中国汉族人群非综合征型唇腭裂发病风险的关联  

Association study between haplotypes of WNT signaling pathway genes and non-syndromic oral clefts among Chinese Han populations

作　　者：王梦莹[1] 李文咏 周仁 王斯悦 刘冬静[1] 郑鸿尘 周治波[2] 朱洪平[2] 吴涛[1] 胡永华[1] WANG Meng-ying;LI Wen-yong;ZHOU Ren;WANG Si-yue;LIU Dong-jing;ZHENG Hong-chen;ZHOU Zhi-bo;ZHU Hong-ping;WU Tao;HU Yong-hua(Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China;Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Research Center of Engineering and Technology for Computerized Dentistry & NMPA Key Laboratory for Dental Materials, Beijing 100081, China)

机构地区：[1]北京大学公共卫生学院流行病与卫生统计学系,北京100191 [2]北京大学口腔医学院·口腔医院口腔颌面外科,国家口腔医学中心,国家口腔疾病临床医学研究中心,口腔生物材料和数字诊疗装备国家工程研究中心,口腔数字医学北京市重点实验室,国家卫生健康委员会口腔医学计算机应用工程技术研究中心,国家药品监督管理局口腔生物材料重点实验室,北京100081

出　　处：《北京大学学报（医学版）》2022年第3期394-399,共6页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金(81102178、81573225);北京市自然科学基金(7172115)。

摘　　要：目的:拟在1008个中国人群非综合征型唇腭裂(non-syndromic oral clefts,NSOC)核心家系中探索WNT信号通路相关基因位点单体型在疾病发生风险中的作用。方法:本研究数据来自一项全基因组关联研究(genome-wide association study,GWAS),研究人群为“唇腭裂基因和交互作用的国际合作研究”项目在中国地区募集的806个非综合征型唇裂合并或不合并腭裂(non-syndromic cleft lip with or without cleft palate,NSCL/P)核心家系和202个非综合征型单纯腭裂(non-syndromic cleft palate,NSCP)核心家系。分别在NSCL/P和NSCP家系中,通过传递不平衡检验(transmission disequilibrium test,TDT)探索基因单体型与疾病的关联。经过Bonferroni多重检验校正后,统计学检验的显著性阈值均设为P<3.47×10^(-4)。单体型关联分析通过plink(v1.07)软件完成。结果:经过数据质量控制后,NSCL/P核心家系和NSCP核心家系各纳入7个基因上的144个单核苷酸多态性(single nucleotide polymorphisms,SNPs)位点进行分析。NSCL/P家系中69个单体型与NSCL/P存在关联(P<0.05),NSCP家系中34个单体型与NSCP存在关联(P<0.05),但经过Bonferroni多重检验校正后,关联均不具有统计学意义(P>3.47×10^(-4))。结论:未发现WNT信号通路相关基因位点单体型在NSCL/P和NSCP发病风险中的作用。Objective:To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts(NSOC)based on haplotypes analyses among 1008 Chinese NSOC case-parent trios.Methods:The genome-wide association study(GWAS)data of 806 Chinese non-syndromic cleft lip with or without cleft palate(NSCL/P)trios and 202 Chinese non-syndromic cleft palate(NSCP)case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts(ICOCs)study GWAS data set,whose Chinese study population were recruited from four provinces in China,namely Taiwan,Shandong,Hubei,and Sichuan provinces.The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University,using Illumina Human610-Quad v.1_B Bead Chip.The method of sliding windows was used to determine the haplotypes for analyses,including 2 SNPs haplotypes and 3 SNPs haplotypes.Haplotypes with a frequency lower than 1%were excluded for further analyses.To further assess the association between haplotypes and NSOC risks,and the transmission disequilibrium test(TDT)was performed.The Bonferroni method was adopted to correct multiple tests in the study,with which the threshold of statistical significance level was set as P<0.05 divided by the number of tests,e.g P<3.47×10^(-4) in the current stu-dy.All the statistical analyses were performed by using plink(v1.07).Results:After quality control,a total of 144 single nucleotide polymorphisms(SNPs)mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios.A total of 1042 haplotypes with frequency higher than 1%were included for NSCL/P analyses and another 1057 haplotypes with frequency higher than 1%were included for NSCP analyses.Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese(P<0.05).Another 34 haplotypes showed nominal significant association with the NSCP risk among Ch

关 键 词：非综合征型唇腭裂 WNT信号通路 单体型 病例-双亲设计 

分 类 号：R181.2[医药卫生—流行病学]