Developmental Genetic Epidemiology of Smoking

描述(由申请者提供)：这个项目旨在通过研究个人和背景的影响来增加我们对吸烟的病因、发展、异质性和共病的理解。它侧重于青少年，他们是吸烟开始(SI)的最大风险者，在他们中，预防和控制持续吸烟(SP)将对公众健康具有最大的潜在好处。在过去的十年里，复杂性状的定量统计方法和大量遗传信息丰富的流行病学样本取得了巨大的增长，这使得我们能够测试关键的复杂问题。我们可以访问三个关于青春期双胞胎及其父母的纵向遗传信息数据集，六个包含已公布的青少年吸烟数据的数据集，以及三个扩展双胞胎(ET)亲属关系研究。关于吸烟行为的详细数据可以在一名成年人和三名青少年/青年双胞胎样本中获得。数据来自美国、比利时、荷兰、芬兰、澳大利亚和瑞典。我们将检验以下关于SI的假说：1)青春期早期的SI主要受共同环境因素的影响；遗传因素在青春期后期和青春期对SI的易感性逐渐增加，2)SI的发生率因文化的不同而不同(美国、欧洲、澳大利亚)，但方差成分不同，3)父母和父母吸烟的影响减小，兄弟姐妹和同龄人的影响从青春期到青春期增加，4)测量的环境因素的影响随着青春期逐渐减少，测量的基因(在GWAS中鉴定)的影响随着环境因素的变化而增加，5)测量的基因对SI的影响随环境因素(GxE)的变化而变化，6)基因和环境的作用对于男性和女性是相同的。第二组假设涉及SI与SP/尼古丁依赖(ND)之间的关系。我们将测试7)青春期/青春期SI与SP和ND的测量之间是否存在显著但不完全的遗传和环境重叠，8)SP/ND的年龄和性别存在显著的测量差异，9)相同的基因和环境影响整个青春期的SI和SP，10)SI、SI的发病年龄和发病年龄与SP/ND之间存在遗传重叠，11)环境危险因素对SI的贡献大于SP/ND，12)所测量的基因对SP/ND的贡献大于对SI的贡献。我们获得了丰富的发展(前瞻性和回溯性)数据集，以及我们在遗传信息样本统计建模方面的专业知识，这使我们处于解决这些特定目标的独特和理想的地位。这样做将大大提高对先天和后天如何相互作用从而产生吸烟倾向的理解。 与公共健康相关：这个项目旨在增加我们对吸烟的病因、发展、异质性和共病的了解，在美国，吸烟仍然是主要的可预防的死亡原因，约占1例或每5例死亡。我们将重点关注个人和背景的影响，以期在预防和控制吸烟行为方面取得进展，从而影响公众健康。

DESCRIPTION (provided by applicant): This project aims to increase our understanding of the etiology, development, heterogeneity and comorbidity of smoking by examining both individual and contextual influences. It focuses on adolescents, who are at greatest risk for smoking initiation (SI) and in whom prevention and control of smoking persistence (SP) would have the greatest potential benefit to public health. The last decade has seen tremendous growth in quantitative statistical methods for complex traits, and in large genetically informative epidemiological samples, which now allow us to test critical complex questions. We have access to three longitudinal genetically informative data sets of adolescent twins and their parents, six data sets with published adolescent smoking data and three extended twin (ET) kinship studies. Detailed data on smoking behavior are available in one adult and in three adolescent/young adult twin samples. Data are from the United States, Belgium, the Netherlands, Finland, Australia and Sweden. We will test the following hypotheses about SI: 1) SI in early adolescence is primarily influenced by shared environmental factors; genetic factors gradually contribute more to liability to SI in later adolescence and young adulthood, 2) the rates of SI vary by culture (US, Europe, Australia), but variance components do not, 3) the influence of parents and parental smoking decreases and that of siblings and peers increases from adolescence to young adulthood, 4) the influence of measured environmental factors gradually decreases and that of measured genes (identified in GWAS) increases over adolescence, 5) the effect of measured genes on SI varies as a function of environmental factors (GxE), 6) the role of genes and environment is the same for males and females. The second set of hypotheses concerns the relationship between SI and SP/ nicotine dependence (ND). We will test whether 7) there is significant but not complete genetic and environmental overlap between SI and measures of SP & ND in adolescence/ young adulthood, 8) there is significant measurement variance by age and sex for SP/ND, 9) the same genes and environments influence SI and SP throughout adolescence, 10) there is genetic overlap between SI, age of onset of SI and between age of onset and SP/ND, 11) the contribution of environmental risk factors is greater to SI than to SP/ND, and 12) the contribution of measured genes (identified in GWAS) is greater for SP/ND than for SI. Our access to rich developmental (prospective and retrospective) data sets and our expertise in statistical modeling of genetically informative samples, puts us in a unique and ideal position to address these specific aims. Doing so will substantially improve understanding of how nature and nurture interact to generate liability to smoking. PUBLIC HEALTH RELEVANCE: This project aims to increase our understanding of the etiology, development, heterogeneity and comorbidity of smoking, which remains the leading preventable cause of death in the US, accounting for approximately 1 or ever 5 deaths. We will focus on both individual and contextual influences in order to make progress in prevention and control of smoking behavior, and thus influence public health.