Genetic Epidemiology of HIV Risk Behavior Trajectory in the ALIVE Cohort

ALIVE 队列中 HIV 风险行为轨迹的遗传流行病学

• 批准号: 8634089
• 负责人: Brion S Maher
• 金额: $ 16.2万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8634089
• 关键词: AIDS prevention; Acquired Immunodeficiency Syndrome; Addictive Behavior; Address; Adoption; Affect; African American; Age; Anxiety; Baltimore; Behavior; Behavior Disorders; Behavioral; Biological; Biological Assay; Communities; Dependence; Dimensions; Drug Addiction; Drug Use Disorder; Drug usage; Drug user; Enrollment; Environment; Family; Funding; Future; Genes; Genetic; Genetic Risk; Genome; Genotype; Goals; HIV; HIV Infections; HIV risk; Heritability; Infection; Injecting drug user; Injection of therapeutic agent; Intravenous; Investigation; Length; Link; Longitudinal Studies; Measures; Mental Depression; Metric; Molecular Genetics; National Institute of Drug Abuse; Neighborhoods; Neurobiology; Pathway interactions; Pattern; Pharmaceutical Preparations; Phenotype; Population; Predisposition; Prevention; Prevention strategy; Preventive Intervention; Relative (related person); Research; Resources; Risk; Risk Behaviors; Sampling; Severities; Sex Behavior; Single Nucleotide Polymorphism; Source; Staging; System; Twin Multiple Birth; Variant; Work; addiction; base; career; cohort; cost; cost effective; design; experience; follow-up; genetic epidemiology; genome wide association study; indexing; injection drug use; innovation; intravenous drug use; intravenous drug user; intravenous injection; novel; prospective; public health relevance; risk sharing; success; treatment strategy

DESCRIPTION (provided by applicant): Among HIV risk behaviors, those related to intravenous drug use are the most salient, with sero-conversion rates among intravenous drug users of at least 6.2%. Importantly, other behavioral dimensions, primarily related to impulse control, are correlated, jointly influence HIV infection risk and share an underlying neurobiology. The AIDS Linked to the Intravenous Experience (ALIVE) is a prospective community-based cohort of intravenous drug users (IDUs) in Baltimore that commenced in 1988, eventually enrolling more than 3,500 IDUs. Semi-annual follow-up included comprehensive assessment of risk behaviors and drug use. A separate study, focused on non-behavioral genetic risk for infection performed a genome-wide association study (GWAS) on a subset (N=1197) of the sample. This will allow us, in an existing, large, well-characterized, predominantly African-American sample, to investigate in a genome-wide association framework the contribution of measured genotypes to variation in HIV behavioral risk trajectory defined using drug and other behavioral-risk measures. In Aim 1, we propose to examine the genetic contribution to class membership in longitudinal intravenous (IV) drug injection trajectories in the already genotyped ALIVE sample. Prior work in this sample has identified unique longitudinal classes of drug injection career. In Aim 2, we will perform a genome-wide association scan of a novel 'injection years' phenotype designed to capture the length of an injector's career. In Aim 3, we will generate a novel composite index of HIV-risk behavior, using drug-related and sexual behaviors. We will examine this novel risk metric in a longitudinal framework and perform a GWAS of HIV-risk trajectory class. Our three Specific Aims leverage this unique, existing, NIDA-funded resource to address novel hypotheses regarding the genetics of HIV risk behaviors without the costs of additional genetic assays. This work is novel, innovative, cost effective and likely to identify important genetic contributions to HIV risk trajectory. The examination of longitudinal intravenous (IV) drug injection trajectories and the genome-wide association scan in the ALIVE sample of a novel 'injection years' and composite HIV risk phenotypes is significant because it will inform prevention and treatment strategies and aid in identifying subpopulations or clusters of behaviors that are more amenable to prevention strategies. In short, the research is significant because the results will elucidate our understanding of modifiable and fixed components of HIV behavior risk trajectories in this and other populations, and leads to enhanced efforts at treatment and prevention.

描述（申请人提供）：在 HIV 危险行为中，与静脉吸毒相关的行为最为突出，静脉吸毒者的血清转化率至少为 6.2%。重要的是，其他行为维度（主要与冲动控制相关）是相关的，共同影响艾滋病毒感染风险并共享潜在的神经生物学。与静脉注射经历相关的艾滋病 (ALIVE) 是巴尔的摩一个基于社区的静脉吸毒者 (IDU) 前瞻性队列，于 1988 年启动，最终招募了超过 3,500 名 IDU。每半年随访一次，包括对危险行为和药物使用的综合评估。另一项针对感染的非行为遗传风险的单独研究对样本的子集 (N=1197) 进行了全基因组关联研究 (GWAS)。这将使我们能够在现有的、大量的、特征明确的、主要是非裔美国人的样本中，在全基因组关联框架中调查测量的基因型对使用药物和其他行为风险定义的艾滋病毒行为风险轨迹变化的贡献措施。在目标 1 中，我们建议检查已基因分型的 ALIVE 样本中纵向静脉 (IV) 药物注射轨迹中类别成员的遗传贡献。该样本之前的工作已经确定了药物注射职业的独特纵向类别。在目标 2 中，我们将对一种新颖的“注射年”表型进行全基因组关联扫描，旨在捕获注射者职业生涯的长度。在目标 3 中，我们将利用毒品相关行为和性行为生成一个新的 HIV 风险行为综合指数。我们将在纵向框架中检查这一新的风险指标，并进行 HIV 风险轨迹类别的 GWAS。我们的三个具体目标利用这一独特的、现有的、由 NIDA 资助的资源来解决有关 HIV 风险行为遗传学的新假设，而无需额外的基因检测成本。这项工作新颖、创新、具有成本效益，并且可能确定对艾滋病毒风险轨迹的重要遗传贡献。 对新型“注射年份”和复合 HIV 风险表型的 ALIVE 样本中纵向静脉 (IV) 药物注射轨迹的检查和全基因组关联扫描具有重要意义，因为它将为预防和治疗策略提供信息，并有助于识别亚群或更适合预防策略的行为群。简而言之，这项研究意义重大，因为研究结果将阐明我们对这一人群和其他人群的艾滋病毒行为风险轨迹的可改变和固定组成部分的理解，并导致加强治疗和预防工作。