Genetic Epidemiology of HIV Risk Behavior Trajectory in the ALIVE Cohort

描述（由申请人提供）：在艾滋病毒风险行为中，与静脉吸毒有关的行为最突出，静脉吸毒者的血清转换率至少为6.2%。重要的是，主要与冲动控制相关的其他行为维度是相关的，共同影响HIV感染风险，并共享潜在的神经生物学。艾滋病与静脉注射经验（ALIVE）是一个前瞻性的社区为基础的队列静脉注射毒品使用者（IDUs）在巴尔的摩，开始于1988年，最终招募了3,500多名IDUs。半年随访包括对危险行为和药物使用的综合评估。一项单独的研究，专注于非行为遗传感染风险，对样本的一个子集（N=1197）进行了全基因组关联研究（GWAS）。这将使我们能够在一个现有的，大的，特征良好的，主要是非洲裔美国人的样本中，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措施定义的HIV行为风险轨迹变化的贡献。在目的1中，我们建议在已经基因分型的ALIVE样本中检查纵向静脉内（IV）药物注射轨迹对类成员资格的遗传贡献。在这个样本中，以前的工作已经确定了独特的纵向药物注射职业类别。在目标2中，我们将对一种新的“注射年”表型进行全基因组关联扫描，该表型旨在捕获注射者职业生涯的长度。在目标3中，我们将使用与毒品有关的行为和性行为，生成一个新的艾滋病毒风险行为复合指数。我们将在纵向框架中研究这种新的风险度量，并执行HIV风险轨迹类的GWAS。我们的三个具体目标利用这一独特的，现有的，NIDA资助的资源，以解决新的假设，对艾滋病毒的风险行为的遗传学，而无需额外的基因检测的成本。这项工作是新颖的，创新的，具有成本效益的，并有可能确定重要的遗传贡献艾滋病毒的风险轨迹。 纵向静脉注射（IV）药物注射轨迹的检查和全基因组关联扫描的一种新的“注射年”和复合艾滋病毒风险表型的ALIVE样本是重要的，因为它将告知预防和治疗策略，并有助于确定亚群或集群的行为，更适合预防策略。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中艾滋病毒行为风险轨迹的可改变和固定成分的理解，并导致加强治疗和预防工作。

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.