Human Genetics of Addiction: A Study of Common and Specific Factors

成瘾给个人和社会带来了巨大的负担，对导致这种疾病的潜在遗传和环境因素的进一步了解将有助于预防和治疗工作。该项目将使用三个大型的遗传信息数据集，包括对物质依赖，共病障碍和环境因素的综合评估：酒精中毒遗传学的合作研究，可卡因依赖的家庭研究和尼古丁依赖的合作遗传研究。该项目有四个目标：目标1：研究三个数据库中的遗传发现，以寻找成瘾发展中的共同和特定因素。遗传学研究结果将在数据集内和数据集之间进行检查，以便更好地了解成瘾发展中的常见和特定遗传因素。目的2：研究精细的表型，如遗传分析中吸烟、酗酒和多物质依赖的定量表型。将对多物质症状计数等定量表型进行改进，以进一步研究遗传多态性和成瘾性。由于这三项研究共享一个共同的评估，这些改进的表型可以应用于所有数据库。目的3：探讨种族、性别和精神共病对“高危”基因型的影响。将检查表型和基因型的相关性，以确定不同的依赖亚型是否与特定的“风险”基因型相关。这将包括按种族、性别、其他物质依赖和精神病合并症进行检查。目标4：通过对多效性、基因-基因和基因-环境相互作用的额外遗传分析，研究物质依赖和数量表型的复杂遗传学。候选人是一名独立的调查员，他已经对成瘾的遗传流行病学研究做出了重要贡献。这个独立科学家奖将使她能够继续从事她对人类成瘾遗传学的研究。她将继续与华盛顿大学和全国的研究人员合作，以便将最先进的方法应用于这种复杂疾病的遗传分析。通过比较和对比三个数据集的结果，将更深入地了解人类成瘾的共同和特定因素。

DESCRIPTION (provided by applicant): Addiction places a tremendous burden on individuals and society, and an improved understanding of the underlying genetic and environmental factors that contribute to this disease will aid prevention and treatment efforts. This project will use three large, genetically informative datasets that include comprehensive assessments of substance dependence, comorbid disorders and environmental factors: the Collaborative Study on the Genetics of Alcoholism, the Family Study of Cocaine Dependence, and the Collaborative Genetic Study of Nicotine Dependence. This project has four aims: Aim 1: To study genetic findings in three databases in the search for common and specific factors involved in the development of addiction. Genetic findings will be examined within and across datasets so that a better understanding of common and specific genetic factors in the development of addiction can be developed. Aim 2: To examine refined phenotypes, such as quantitative phenotypes of smoking, alcoholism, and polysubstance dependence in genetic analyses. The refinement of quantitative phenotypes such as a polysubstance symptom count will be undertaken in order to further the study of genetic polymorphisms and addiction. Because these three studies share a common assessment, these refined phenotypes can be applied to all databases. Aim 3: To examine the influence of ethnicity, gender and psychiatric comorbidity on the "at risk" genotypes. Phenotype and genotype correlations will be examined to determine whether distinct dependence subtypes are associated with specific "at risk" genotypes. This will include an examination by ethnicity, gender, additional substance dependence, and psychiatric comorbidity. Aim 4: To examine complex genetics of substance dependence and quantitative phenotypes using additional genetic analyses of pleiotropy, gene-gene, and gene-environment interactions. The candidate is an independent investigator who has already made important contributions to the study of the genetic epidemiology of addiction. This Independent Scientist Award will allow her to continue to pursue her research on the human genetics of addiction. She will continue to collaborate with investigators at Washington University and nationally in order to apply state of the art approaches to genetic analysis of this complex disorder. By comparing and contrasting findings in three datasets, a more thorough understanding of common and specific factors underlying human addiction will be developed.