Disentangling Substance Use and Psychiatric Disorder Comorbidity for Future HuGE

解开未来 HuGE 的药物使用和精神疾病合并症

• 批准号: 7046288
• 负责人: RUMI KATO PRICE
• 金额: $ 22.95万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7046288
• 关键词: Disentangling; Substance; Use; Psychiatric; Disorder

DESCRIPTION (provided by applicant): There is a rapidly increasing need of public health significance to integrate human genetic information into analyses of population epidemiologic data to provide better understanding of biology-environment mechanisms underlying comorbidity of substance use and psychiatric disorders. In response to RFA-DA- 05-005, this R01 application requests support for 5 years to conduct coordinated analyses of NLAES, NESARC, Add Health and NHSDA/NSDUH repeated cross-sectional and/or longitudinal adolescent and adult national survey datafiles (each with different strengths and weaknesses) to provide informative results for future human-genome epidemiology (HuGE) aspects of NESARC. Race/ethnicity, immigration and acculturation, and family history, as well as gender, are conceptualized as key "low-resolution" genetic-behavioral-social (G-B-S) markers (reflecting molecular evolutionary history and recent population dynamics) to capture the interplay of genetic and environmental etiological factors. The main phenotypes are cross-sectional or longitudinal comorbidity of relatively-common substance use and psychiatric disorders or syndromes; the pleiotropy concept is applied to unrelated individuals. Add Health data with limited candidate gene information will be used to guide analyses for NESARC; when genotype information becomes available from NESARC, a portion of the phenotypic variance across race/ethnicity and individuals should be "explained away" by candidate gene main effects, epistasis, gene -environment interactions, in addition to independent environmental effects already measurable from the current NESARC datafiles. Specific analysis aims are to: 1) select phenotypes suitable for multiple-phenotype analyses by examining race/ethnicity differences on the comorbidity of two disorders that identify phenotypes that are likely to be influenced by relatively new polymorphisms or by relatively localized environmental factors or both; 2) corroborate cross-sectional phenotype selection achieved in Aim 1 from a genetic perspective; 3) delineate major gender- and race-/ethnic-specific environmental influences on the phenotypes selected in Aim 1; 4) improve polygenic measures standing-in for candidate genes for use in Aims 6), 7) and 8); 5) develop pleiotropy models of substance use abuse and psychiatric comorbidity (SAPC) to guide Aims 6), 7), and 8); 6) develop and test cross-sectional pleiotropy models for NESARC including environmental measures identified in Aim 3); 7) develop longitudinal pleiotropy models of SAPC for NESARC; 8) replicate the pleiotropy models developed in Aims 6) and 7) by replacing stand-in polygenic measures with candidate genotypes, pending on the availability of genotype data from NESARC.

描述（由申请人提供）： 人们对公共卫生意义的需求迅速增加，将人类遗传信息整合到人群流行病学数据的分析中，以更好地理解对物质使用和精神疾病的合并症的生物学 - 环境机制。为了响应RFA-DA-05-005，此R01申请要求提供5年的支持，以进行NLAE，NESARC，NESARC，ADD NHSDA/NSDA/NSDA/NSDUH的协调分析，重复的横截面和/或纵向和/或纵向青春期和纵向青春期和成人国家调查（每个人都具有不同的力量和弱点），以提供人类的范围，以提供人类的范围。 nesarc。种族/民族，移民和文化以及家族史以及性别被概念化为关键的“低分辨率”遗传 - 行为社会（G-B-S）标记（反映分子进化史和最近的人口动态），以捕获遗传和环境病理学因素的相互作用。主要表型是相对常见的药物使用以及精神疾病或综合征的横断面或纵向合并症；多效概念应用于无关的个体。添加具有有限候选基因信息的健康数据将用于指导NESARC的分析；当从NESARC获得基因型信息时，除了已经可以从当前NESARC DataFiles可以测量的独立环境效应外，还应通过候选基因主要影响，Epitisis，基因 - 环境相互作用来“解释”跨种族/种族的表型差异的一部分。特定分析的目的是：1）选择适合多种表型分析的表型，通过检查种族/族裔差异在两种疾病的合并症上的种族/族裔差异，这些疾病鉴定出可能受相对新的多态性或相对局部的环境因素或两者或两者都受到相对新的多态性影响的表型。 2）从遗传学角度来证实在目标1中获得的横截面表型选择； 3）描述对AIM 1中选择的表型的主要性别和种族/种族特异性环境影响； 4）改善了候选基因的多基因措施，以用于目标6），7）和8）； 5）开发用于使用滥用和精神合并症的物质的多效模型（SAPC）来指导目标6），7）和8）； 6）为NESARC开发和测试横截面多效模型，包括AIM 3中确定的环境措施； 7）为NESARC开发SAPC的纵向多效模型； 8）复制在目标6）中开发的多效模型和7）通过用候选基因型代替备用多基因措施，待定NESARC的基因型数据的可用性。