Examination of the Involvement of Cholinergic-Associated Genes in Nicotine Behaviors in European and African Americans.
Examination of the Involvement of Cholinergic-Associated Genes in Nicotine Behaviors in European and African Americans.
复制标题
检查欧洲和非裔美国人尼古丁行为中胆碱能相关基因的参与情况。
DOI：
10.1093/ntr/ntw200
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Ehringer,MarissaA
中科院分区：
文献类型：
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作者：
Melroy-Greif,WhitneyE;Simonson,MatthewA;Corley,RobinP;Lutz,SharonM;Hokanson,JohnE;Ehringer,MarissaA
吸烟是一种有害生理的习惯。尼古丁乙酰胆碱受体（nAChR）与尼古丁结合，并在长期暴露于尼古丁时上调。已知这些受体的上调不是由于这些基因的mRNA的变化，然而，关于该过程的更精确的细节仍然不确定，有几种合理的假设描述了nAChR如何上调。我们已经手动策划了一组被认为在尼古丁诱导的nAChR上调中发挥作用的基因。在这里，我们测试的假设，这些基因与尼古丁依赖（ND）和每天吸烟（CPD）的数量相关，并有助于风险。（选举机构和行政机构，分别）收集和基因-结果虽然有几个新的基因与CPD和ND相关，但P <0.05。在EA和AA中，0.05，这些关联在多次检验的校正中没有存活。以前的协会之间CHRNA 3，CHRNA 5，CHRNB 4和CPD在EAs replicated.ConclusionsOur假设驱动的方法避免了许多固有的局限性，在途径分析和提供名义证据胆碱能相关基因和尼古丁behaviors.ImplicationsWe评估的证据之间的关联手动策划的一组基因和尼古丁行为在欧洲和非洲裔美国人。虽然在多次测试校正后没有基因相关，但这项研究有几个优点：通过手动管理一组基因，我们规避了许多途径分析中固有的限制，并测试了几个尚未在人类遗传学研究中检测的基因;基于基因的测试是测试与一组基因相关性的有用方法;这些基因是根据文献回顾和与专家交谈收集的，强调了科学合作的重要性。
IntroductionCigarette smoking is a physiologically harmful habit. Nicotinic acetylcholine receptors (nAChRs) are bound by nicotine and upregulated in response to chronic exposure to nicotine. It is known that upregulation of these receptors is not due to a change in mRNA of these genes, however, more precise details on the process are still uncertain, with several plausible hypotheses describing how nAChRs are upregulated. We have manually curated a set of genes believed to play a role in nicotine-induced nAChR upregulation. Here, we test the hypothesis that these genes are associated with and contribute risk for nicotine dependence (ND) and the number of cigarettes smoked per day (CPD).MethodsStudies with genotypic data on European and African Americans (EAs and AAs, respectively) were collected and a gene-based test was run to test for an association between each gene and ND and CPD.ResultsAlthough several novel genes were associated with CPD and ND atP< 0.05 in EAs and AAs, these associations did not survive correction for multiple testing. Previous associations betweenCHRNA3, CHRNA5,CHRNB4and CPD in EAs were replicated.ConclusionsOur hypothesis-driven approach avoided many of the limitations inherent in pathway analyses and provided nominal evidence for association between cholinergic-related genes and nicotine behaviors.ImplicationsWe evaluated the evidence for association between a manually curated set of genes and nicotine behaviors in European and African Americans. Although no genes were associated after multiple testing correction, this study has several strengths: by manually curating a set of genes we circumvented the limitations inherent in many pathway analyses and tested several genes that had not yet been examined in a human genetic study; gene-based tests are a useful way to test for association with a set of genes; and these genes were collected based on literature review and conversations with experts, highlighting the importance of scientific collaboration.