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浙江大学学报（农业与生命科学版）
浙江大学学报(农业与生命科学版)  2014, Vol. 40 Issue (4): 413-420    DOI: 10.3785/j.issn.1008-9209.2014.04.214
论文     
吸烟对控制FEV1/FVC比率的基因上位性及性别互作效应的影响(英文)
许昌巍1， 朱军1,2,3*
（1.浙江大学数学系，杭州 310058；2.浙江大学农业与生物技术学院农学系，杭州 310058；3.浙江大学空气污染与健康研究中心，杭州 310058）
Impacts of cigarette smoking on epistasis and gender-specific effects of FEV1/FVC ratio in human
Xu Changwei1, Zhu Jun1,2,3*
(1. Department of Mathematics, Zhejiang University, Hangzhou 310058, China; 2. Department of Agronomy, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China; 3. Research Center for Air Pollution and Health, Zhejiang University, Hangzhou 310058, China)
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摘要： 1秒呼出气体体积（forced expiratory volume in one second，FEV1）与最大肺活量（forced vital capacity，FVC）是肺部活动的重要指标.FEV1/FVC指数是诊断肺部疾病的重要指标，与基因、性别、吸烟和空气污染有关.本文基于dbGaP数据库下载的不同民族人群疾病性状基因组和表现型数据，运用我们提出的混合线性模型方法和关联分析软件QTXNetwork，对FEV1/FVC指数的遗传变异进行了全基因组关联分析.在561 467个单核苷酸多态性中，发现12个显著的数量性状SNPs (quantitative trait with single nucleotide polymorphisms，QTSs)，并运用我们研制的BiopubInfo搜索工具验证了每个QTS的基因功能及其与肺功能之间的关系.结果表明：基因STIM2和MRE11A（PEW值<1×10-5）与慢性阻塞性肺病高度关联；基因APOL3（PEW值<1×10-5）的影响因不同性别而异，以往的研究也检测到该基因与吸烟的关联；基因MRE11A和DNAJC15与肺腺癌存在关联，这是慢性阻塞性肺病的严重并发症.检测到显著的基因上位性效应,揭示了控制复杂性状基因功能的多效性；遗传关联结果揭示了遗传效应与环境因素的关系，为检测和治疗慢性阻塞性肺病和其他呼吸系统疾病提供了潜在新途径.
Abstract: The ratio of FEV1 (forced expiratory volume in one second) to FVC (forced vital capacity) is an index for pulmonary obstruction measurement and one of the most significant predictors for chronic obstructive pulmonary disease (COPD), which is a heritable multi-factorial disease. We present genome-wide association study (GWAS) to map the genetic architecture of this trait and investigate the networks between the external factors (smoking and gender) and genetic factors. By using a mixed linear model and a conditional model, we conducted GWAS in a cohort suffered COPD from the U.S. National Heart, Lung and Blood Institute. Among 561 467 single nucleotide polymorphisms, we found 12 significant quantitative trait SNPs (QTSs) fitted the full model. And for each of them, we demonstrated the mechanisms and relationship between pulmonary function and genes detected. STIM2 and MRE11A (PEW-value<1×10-5) showed unambiguous evidence of association with COPD. APOL3 (PEW-value<1×10-5) was influenced by different genders in different ways and previous studies also implicated its associations with smoking behavior. The variation of genes MRE11A and DNAJC15 was related to lung adenocarcinoma, which is a serious complication of COPD. The significant epistasis effects of these genes suggested the possibility of multiple functional polymorphisms. These associations offer mechanistic insight into pulmonary function regulation and networks between genetics factors and environmental factors, which indicate potential ways for interventions to COPD and many other respiratory diseases.
出版日期: 2014-07-20
CLC:  Q 811.4  
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许昌巍
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引用本文:

许昌巍， 朱军. 吸烟对控制FEV1/FVC比率的基因上位性及性别互作效应的影响(英文)[J]. 浙江大学学报(农业与生命科学版), 2014, 40(4): 413-420.

Xu Changwei, Zhu Jun. Impacts of cigarette smoking on epistasis and gender-specific effects of FEV1/FVC ratio in human. Journal of Zhejiang University (Agriculture and Life Sciences), 2014, 40(4): 413-420.

链接本文:

http://www.zjujournals.com/agr/CN/10.3785/j.issn.1008-9209.2014.04.214    或    http://www.zjujournals.com/agr/CN/Y2014/V40/I4/413

[1] 郝心颖， 朱军. 全基因组关联分析SGRQ遗传变异与吸烟的关系(英文)[J]. 浙江大学学报(农业与生命科学版), 2014, 40(4): 431-439.
[2] 张斌， 朱军. 吸烟和性别对身体质量指数遗传结构的影响(英文)[J]. 浙江大学学报(农业与生命科学版), 2014, 40(4): 421-430.