Interaction between polygenic risk for cigarette use and environmental exposures in the Detroit Neighborhood Health Study.
Interaction between polygenic risk for cigarette use and environmental exposures in the Detroit Neighborhood Health Study.
复制标题
DOI：
10.1038/tp.2013.63
复制
发表时间：
2013-08-13
影响因子：
6.8
通讯作者：
Koenen KC
中科院分区：
文献类型：
--
作者：
Meyers JL;Cerdá M;Galea S;Keyes KM;Aiello AE;Uddin M;Wildman DE;Koenen KC
吸烟受遗传和环境因素的影响。直到今年，所有关于吸烟的大规模基因鉴定研究都是在欧洲血统的人群中进行的。因此，吸烟的遗传结构在其他人群中没有得到很好的描述。此外，尽管有丰富的流行病学文献关注吸烟的社会决定因素，但很少有研究调查非裔美国人吸烟的遗传影响（例如，基因-环境相互作用）的调节。在底特律社区健康研究（DNHS）中，我们随机选择了底特律的大多数非裔美国居民作为样本，构建了遗传风险评分（GRS），其中我们结合了最近在大量非裔美国人样本中进行的荟萃分析中的顶级（p值<5 × 10−7）遗传变异。使用回归（有效n=399），我们首先测试了GRS和每天吸烟之间的关系，试图复制meta分析的结果。其次，我们研究了与三种可能缓和吸烟遗传关联的社会背景的相互作用：创伤事件、邻里社会凝聚力和邻里身体障碍。在曾经吸烟的个体中，GRS显著预测了每天吸烟的数量，占该性状总体方差的约3%。结果表明，创伤性事件数与创伤性事件数之间、社区社会凝聚力与创伤性事件数之间存在显著交互作用；遗传风险和吸烟之间的联系在一生中经历过更多创伤事件的个体中更大，而在社会凝聚力更强的社区中生活的个体中则减弱。这项研究为GRS作为复制常见多基因变异的替代方法以及吸烟行为的基因-环境相互作用提供了支持。此外，本研究表明，环境因素有可能加剧（创伤性事件）和减少（邻里社会凝聚力）遗传对吸烟行为的影响。
Cigarette smoking is influenced both by genetic and environmental factors. Until this year, all large-scale gene identification studies on smoking were conducted in populations of European ancestry. Consequently, the genetic architecture of smoking is not well described in other populations. Further, despite a rich epidemiologic literature focused on the social determinants of smoking, few studies have examined the moderation of genetic influences (for example, gene–environment interactions) on smoking in African Americans. In the Detroit Neighborhood Health Study (DNHS), a sample of randomly selected majority African American residents of Detroit, we constructed a genetic risk score (GRS), in which we combined top (P-value <5 × 10−7) genetic variants from a recent meta-analysis conducted in a large sample of African Americans. Using regression (effective n=399), we first tested for association between the GRS and cigarettes per day, attempting to replicate the findings from the meta-analysis. Second, we examined interactions with three social contexts that may moderate the genetic association with smoking: traumatic events, neighborhood social cohesion and neighborhood physical disorder. Among individuals who had ever smoked cigarettes, the GRS significantly predicted the number of cigarettes smoked per day and accounted for ∼3% of the overall variance in the trait. Significant interactions were observed between the GRS and number of traumatic events experienced, as well as between the GRS and average neighborhood social cohesion; the association between genetic risk and smoking was greater among individuals who had experienced an increased number of traumatic events in their lifetimes, and diminished among individuals who lived in a neighborhood characterized by greater social cohesion. This study provides support for the utility of the GRS as an alternative approach to replication of common polygenic variation, and in gene–environment interaction, for smoking behaviors. In addition, this study indicates that environmental determinants have the potential to both exacerbate (traumatic events) and diminish (neighborhood social cohesion) genetic influences on smoking behaviors.
登录
查看更多内容
影响因子：
0.9
作者：
Eaves, LJ
通讯作者：
Eaves, LJ
DOI：
10.1111/j.1530-0277.2009.01011.x
发表时间：
2009-10-01
影响因子：
3.2
作者：
Dick, Danielle M.;Bernard, Matthew;Rose, Richard J.
通讯作者：
Rose, Richard J.
影响因子：
6.9
作者：
Lessov, CN;Martin, NG;Madden, PAF
通讯作者：
Madden, PAF
影响因子：
2.6
作者：
Boardman, Jason D.;Saint Onge, Jarron M.;Hewitt, John K.
通讯作者：
Hewitt, John K.
影响因子：
0.9
作者：
Broms, U;Silventoinen, K;Kaprio, J
通讯作者：
Kaprio, J