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Genome-Wide Association Study of Heroin Abuse: A Multiethnic Study

海洛因滥用的全基因组关联研究：一项多种族研究

基本信息

批准号：
8325514
负责人：
Eric Otto Johnson
金额：
$ 39.28万
依托单位：
RESEARCH TRIANGLE INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8325514
关键词：
Accounting Address Admixture Adult Affect African American Age American Australia Biological Biology Candidate Disease Gene Case Study Caucasians Caucasoid Race Chinese People Clinical Cohort Studies Complex Confidential Information Conflict (Psychology)Controlled Study DRD2 gene DRD4 gene DSM-IV Data Data Analyses Data Set Dependence Detection Development Disease Dopamine Receptor Drug Controls Drug abuse Drug usage Ensure Environment Epidemiological Factors Ethnic Origin Ethnic group Evaluation Foundations Genes Genetic Genetic Determinism Genetic Heterogeneity Genetic Research Genetic Risk Genomics Genotype Goals Grant HIV HIV-1 Health Heroin Heroin Abuse Human Individual Infection Information Networks Injecting drug user Injection of therapeutic agent Instruction Letters Linkage Disequilibrium Maps Measures Metadata Methods Minority Molecular Genetics National Human Genome Research Institute National Institute of Drug Abuse Nicotine Dependence Non-Insulin-Dependent Diabetes Mellitus North America Opiate Addiction Opioid Participant Pathway interactions Persons Pharmacogenetics Phase Phenotype Policies Population Procedures Publishing Race Receptor Gene Recruitment Activity Reporting Research Research Personnel Resources Risk Running Sample Size Sampling Sampling Studies Scanning Severities Single Nucleotide Polymorphism Site Societies Source Substance abuse problem Surveys TCF7L2 gene Testing Time United States National Institutes of Health Urban Health Variant Work abstracting addiction base case control caucasian American cohort cost data sharing database of Genotypes and Phenotypes expectation follow-up genetic analysis genetic association genetic variant genome wide association study genome-wide linkage high risk interest meetings opioid abuse repository response success tool

项目摘要

PROJECT SUMMARY/ABSTRACT DESCRIPTION: See instructions. This must contain a summary of the proposed activity suitable for dissemination to the public (no proprietary/confidential information). It should be a self-contained description of the project and contain a statement of objectives and methods to be employed. It should be informative to other persons working in the same or related fields. DO NOT EXCEED THE SPACE PROVIDED. The overarching goal of this project is to identify and characterize genetic determinants of heroin abuse in large samples of African Americans and Caucasians by conducting (1) a case/control genome-wide association study (GWAS) of heroin abuse; (2) cross-population contrast mapping to help identify causal variants; and (3) replication analyses in independent samples. To achieve this goal we propose to capitalize on our current GWAS of HIV-1 infection among injection drug users (IDUs) (DA026141), and match the Urban Health Study's (UHS) 3,878 African American and 2,685 Caucasian heroin abuse cases to controls from publicly available data. The R21 phase focuses on identifying, obtaining, and matching optimal control subjects to cases. The R33 phase focuses on the genetic analyses of the derived case/control data. GWAS have had a number of replicable successes identifying genetic variants that contribute to the risk for complex diseases including for substance abuse (e.g., CHRNA5 with nicotine dependence). There are few GWAS of substance abuse, particularly for rarer high-risk substance abuse like heroin abuse. Although about 50% of the risk for heroin abuse is attributable to genetic factors and a number of molecular genetic studies have yielded intriguing results, no genetic variants have strongly replicated evidence of contributing to this genetic risk. To address this need, we will pursue the following R21 and R33 aims: Aim 1: To identify, evaluate, and acquire control samples to match to UHS heroin abuse cases for a GWAS. Aim 2: To develop analytic datasets from UHS heroin abuse cases and identified control samples. Aim 3: To evaluate genetic associations for heroin abuse in UHS cases (n=6,563) and derived controls among African Americans and Caucasians. Aim 4: To conduct cross-population contrast mapping of top GWA findings to select single-nucleotide polymorphisms (SNPs) for follow-up. Aim 5: To replicate primary findings in independent cohorts. Matching the 6,563 heroin abuse cases to repository controls, the proposed GWAS will be many times larger than any genetic study of heroin abuse and one of the largest of any drug abuse phenotype, allowing for detection of expected small to modest genetic effects. Thus, this GWAS is likely to discover, and to refine understanding of, genetic variants associated with heroin abuse, provide important clues to the biology of addiction, and indicate targets for further study and development of pharmacogenetic treatments.

项目总结/文摘