Evidence for gene-environment interactions in a linkage study of asthma and smoking exposure
Evidence for gene-environment interactions in a linkage study of asthma and smoking exposure
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DOI：
10.1067/mai.2003.170
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发表时间：
2003-04-01
影响因子：
14.2
通讯作者：
Cox, NJ
中科院分区：
文献类型：
--
作者：
Colilla, S;Nicolae, D;Cox, NJ
背景：哮喘是一种常见的慢性呼吸道疾病，其病因是多方面的，包括遗传和环境因素。因此，对影响哮喘易感性的基因进行定位一直是一个挑战。目的：本研究验证了将环境烟草烟雾（ETS）暴露作为哮喘的一个潜在危险因素纳入研究的假设，这将提高对哮喘基因定位的能力。通过使用来自哮喘遗传学合作研究的144个白色家庭，将婴儿期暴露于ETS的环境信息纳入全基因组多点连锁分析。通过模拟方法对观察到的基因-环境相互作用的统计学意义进行了评估。结果：当根据ETS暴露分层时，确定了三个具有名义证据的区域（P < .01），并显示出较基线lod评分显著增加（在97 cM处的1 p，D1 S1669-D1 S1665;在135 cM处的5 q，D5 S1505-D5 S816;和在106 cM处的9 q，D9 S910;所有P <0.05）。此外，其他2个地区，尽管在基于ETS暴露分层后未达到名义显著性，但在考虑ETS时，显示出较基线lod评分显著增加（240 cM处的1 q，D1 S549; 3 cM处的17 p，D17 S1308;均P < .01）。这些结果说明了哮喘联系的证据如何依赖于暴露于环境因素，如ETS。未来的连锁分析应包括哮喘的可疑环境因素的信息，以帮助靶向新的候选哮喘易感基因。
Background: Asthma, a common and chronic disease of the airways, has a multifactorial cause involving both genetic and environmental factors. As a result, mapping genes that influence asthma susceptibility has been challenging.Objective: This study tests the hypothesis that inclusion of exposure to environmental tobacco smoke (ETS), a potential risk factor for asthma, would improve the ability to map genes for asthma.Methods: By using 144 white families from the Collaborative Study for the Genetics of Asthma, environmental information about exposure to ETS during infancy was incorporated into a genome-wide multipoint linkage analysis. Statistical significance of observed gene-environment interactions was assessed by means of simulation.Results: Three regions with nominal evidence for linkage when stratified on the basis of ETS exposure were identified (P < .01) and showed a significant increase from the baseline lod score (1p at 97 cM, D1S1669-D1S1665; 5q at 135 cM, D5S1505-D5S816; and 9q at 106 cM, D9S910; all P < .05). In addition, 2 other regions, although not meeting nominal significance after stratification on the basis of ETS exposure, showed a significant increase from baseline lod score when ETS was taken into account (1q at 240 cM, D1S549; 17p at 3 cM, D17S1308; all P < .01).Conclusion: These results illustrate how evidence for linkage of asthma can depend on exposure to an environmental factor, such as ETS. Future linkage analyses should include information on suspected environmental factors for asthma to help target new candidate susceptibility genes for asthma.