全基因组关联分析SGRQ遗传变异与吸烟的关系(英文)

Genome-wide association studies for identifying genetic architecture of SGRQ in smoking population

慢性阻塞性肺病作为人类第四大疾病,它的遗传倾向和性别影响一直是热门话题,而吸烟被认为是肺疾病的主要危险因素.本文基于从dbGaP下载的数据,运用我们提出的混合线性模型方法和关联分析软件QTLNetwork,分析了慢性阻塞性肺病复杂性状的遗传变异.运用全基因组关联条件定位的方法,检测到与吸烟无关的8个基因(CSMD1,CAPN8,TNS1,LOC643037,LRFN2,DGKH,FOXL1,DNAH11)、被吸烟诱导的6个基因(CSMD1,CNTNAP5,DGKH,MACROD2,CNIH3,DNAH11)和被吸烟抑制的5个基因(GSDMC,DGKH,LINC00426,METTL4,BMP2)及1对上位基因(CSMD1,LOC643037).其中,具有显著的高遗传性的基因有TNS1,DGKH,MACROD2,CNIH3,LINC00426,METTL4和GSDMC.讨论了吸烟及性别对SGRQ疾病基因表达的影响.

The dualism of genetic predisposition and gender influences has long been a hot topic in the development of chronic obstructive pulmonary disease （ COPD） , and smoking is considered a primary risk factor for this lung disease . This paper aimed to detect susceptibility genes for COPD with the data downloaded from dbGaP . A linear mixed model was employed to conduct association-mapping QTSs （ quantitative trait single-nucleotide polymorphisms） because of its effectiveness in unbiased estimation of random effects with unbalanced data and in controlling population stratification . The primary focus of the study is to identify genetic risk factors that determine susceptibility for COPD and COPD-related phenotypes with the goal of providing insight into clinically relevant COPD subtypes . By comparing the conditional model excluding the cofactor smoking with the full model , we can detect related QTSs , which will reveal the gene expression on COPD caused or suppressed by smoking . As a result , there are significant genes with high heritability ： TNS1 and DGK H were not caused by smoking , MACROD2 and CNIH3 were due to smoking , and LINC00426 , METTL4 and GSDMC were suppressed by smoking .