CDH1基因和IRF6基因在亚洲人群中与非综合征型唇腭裂关联的再分析  

A reanalysis of association of CDH1 and IRF6 genes with non-syndromic cleft lip with or without cleft palate in Asian populations

作　　者：李梦颖 王红[1] LI Mengying;WANG Hong(Department of Biostatistics,School of Public Health,Peking University,Beijing 100191,China)

机构地区：[1]北京大学公共卫生学院生物统计系,北京100191

出　　处：《中国优生与遗传杂志》2021年第6期774-780,共7页Chinese Journal of Birth Health & Heredity

基　　金：国家重点研发计划(2017YFC0907804);国家自然科学基金(81273164)。

摘　　要：目的探索CDH1基因常见变异、其与IRF6基因间交互作用对亚洲人群非综合征型唇裂伴或不伴腭裂(NSCL/P)患病风险的影响。方法对一项唇腭裂国际合作项目的全基因组关联研究的数据进行再分析,选择其中895个亚洲人群完整NSCL/P核心家系,通过基因型传递不平衡检验(TDT)、以基因为基础的关联分析(VEGAS)及单体型分析来探索CDH1常见变异与NSCL/P患病风险的关联,应用Cordell提出的条件Logistic回归模型分析CDH1与IRF6基因间交互作用与NSCL/P的关联。结果两个家系因患儿父亲的基因型缺失率大于5%被剔除,最终样本量为893个完整NSCL/P核心家系,CDH1的全部17个位点及IRF6的全部7个位点均通过了质量控制并纳入相应的分析。基因型TDT结果显示,CDH1基因的rs2902185和rs8061932在加性及显性模型下均与NSCL/P存在关联(P<0.05),rs12597188在加性模型下与NSCL/P存在关联(P<0.05),上述关联经Bonferroni多重检验校正后均无统计学意义(P>0.003),其余位点在加性、显性及隐性模型下均未发现其与NSCL/P相关。以基因为单位的VEGAS分析未发现CDH1基因与NSCL/P相关(P=0.073)。单体型分析得到20种碱基组合与NSCL/P关联达到名义统计学意义(P<0.05),Bonferroni校正后,这些关联均不具有统计学意义。基因间交互作用分析发现CDH1与IRF6的5对位点间交互作用具有名义统计学意义(P<0.05),也均未通过Bonferroni校正。结论对Illumina 610k芯片已测定单核苷酸多态性(SNPs)的分析,未发现CDH1基因常见变异与NSCL/P存在关联,也未发现影响NSCL/P患病风险的CDH1-IFR6基因间交互作用。Objective To explore the effect of single nucleotide polymorphisms(SNPs)in CDH1 and their interactions with SNPs in IRF6 on the risk of non-syndromic cleft lip with or without cleft palate(NSCL/P)in Asian populations.Methods 895 complete NSCL/P trios of Asian ancestry were drawn by an international consortium,which conducted a genome-wide association study to find genes influencing risk to NSCL/P using a case-parent trio design.The genotypic transmission disequilibrium test(TDT)via the trio package in R,gene-based association analysis using VEGAS(versatile gene-based association study)and haplotype analysis through log-linear model in the Haplin package of R were performed to explore the association between SNPs of CDH1 and the risk of NSCL/P.Cordell’s method based on conditional logistic regression model was applied to investigate the effects of potential interactions between CDH1 and IRF6 on NSCL/P via the trio package in R.Results Two trios were excluded due to high genotype missing rate of the father(>5%)and thus resulting a final sample size of 893 complete NSCL/P trios.All 17 SNPs of CDH1 and all 7 SNPs of IRF6 passed the quality control and were included in the corresponding analysis.For genotypic TDT,although rs2902185 and rs8061932 of CDH1 showed nominal significant association with NSCL/P under additive and dominant models,and rs12597188 under additive model(P<0.05),none of them were significant after strict Bonferroni correction(P>0.05/17).Besides,there is no signal of association under recessive model.Gene-based test using VEGAS found no association between CDH1 and NSCL/P(P=0.073).For haplotype analysis,20 haplotypes in CDH1 yielded nominal significant association with NSCL/P,where the most significant evidence was seen in a four-SNP haplotype(A-C-C-A for rs2276330-rs1801552-rs8061932-rs9927789)yielding a P=0.003,however it didn’t pass strict Bonferroni correction(P>0.05/17).Tests for gene-gene interaction identified 5 pairs of nominally significant interactions between CDH1 and IRF6,but none of

关 键 词：CDH1 遗传关联研究 基因间交互作用 唇裂 腭裂 

分 类 号：R782.2[医药卫生—口腔医学]