Genetics of Alcohol Dependence in African Americans: Recruitment

非裔美国人酒精依赖的遗传学：招募

• 批准号: 9769607
• 负责人: JOEL GELERNTER
• 金额: $ 39.55万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9769607
• 关键词: Acute; Address; Affect; African; African American; Alcohol Withdrawal Delirium; Alcohol dependence; Alcohol withdrawal syndrome; Chromosome Mapping; Clinical; Collection; Communities; Comorbidity; Complex; Dangerousness; Data; Diagnosis; Ethics; Funding; Future; Genes; Genetic; Genomic Segment; Genomics; Genotype; Heritability; Individual; Investigation; Medical; Outcome; Pennsylvania; Phenotype; Population; Recording of previous events; Reporting; Research Project Grants; Resources; Sampling; Sampling Studies; Societies; Substance Use Disorder; Time; United States; Universities; Variant; Work; alcohol effect; alcohol risk; base; cost; follow-up; genome wide association study; genome-wide; high risk sexual behavior; improved; recruit; risk variant; study population; trait

ABSTRACT Prevalent alcohol dependence (AD) in the United States, which has increased substantially over the past decade, is highly destructive and costly to individuals and to society. It is also moderately heritable. Delirium tremens (DTs) is a frequent, and often dangerous, consequence of acute alcohol withdrawal. We previously conducted an AD research project focused on the understudied African-American (AA) population and carried out numerous investigations including a pioneering genomewide association study (GWAS) of AD. We also reported GWAS of numerous related traits. Our findings included genomewide significant (GWS) risk loci associated to AD and related traits; our preliminary data support a risk locus for DTs at UNC13C (P= 9.4×10[-9]). Many significant findings, including the DT association, are seen exclusively in AAs. Additional recruitment of AA AD subjects with a state-of-the-art assessment is necessary. Deep phenotyping will make available other relevant related phenotypes, such as risky sexual behavior. New recruitment will build upon our existing sample to increase gene-mapping power not just for AD, but also for other substance use disorder (SUD) traits that are highly comorbid with AD in clinical populations. This resource will enable replication and a more detailed and broader investigation of identified associations. The focus on AA subjects will (a) help to address the well-recognized disparity in complex trait studies of this population; (b) allow us to follow-up GWAS results in the specific population where most of our significant results have been observed (pending future funding); and (c) increase power through greater homogeneity of the study sample. Our new subjects (pending future projects to allow genotyping and analysis based on the subjects to be collected here) will be added to the Psychiatric Genomics Consortium sample to improve the power of their SUD mega-analyses.

摘要 在美国，酒精依赖（AD）在过去十年中大幅增加，对个人和社会具有高度的破坏性和代价。它也是适度遗传的。谵妄是急性酒精戒断的常见且危险的后果。我们以前进行了一个AD研究项目，重点是未充分研究的非洲裔美国人（AA）人群，并进行了大量的调查，包括开创性的AD全基因组关联研究（GWAS）。 我们还报告了许多相关性状的GWAS。我们的研究结果包括与AD和相关性状相关的全基因组显著（GWS）风险位点;我们的初步数据支持在UNC 13 C处存在DT的风险位点（P= 9.4×10[-9]）。许多重要的发现，包括DT协会，只在AA中看到。 需要额外招募AA AD受试者并进行最新技术水平评估。深度表型分析将提供其他相关的相关表型，例如危险的性行为。 新的招募将建立在我们现有的样本，以增加基因图谱的力量，不仅为AD，但也为其他物质使用障碍（SUD）的特点，是高度共病与AD的临床人群。这一资源将有助于对已查明的关联进行复制和更详细、更广泛的调查。对AA受试者的关注将（a）有助于解决这一人群复杂性状研究中公认的差异;（B）使我们能够在观察到我们大多数显著结果的特定人群中随访GWAS结果（等待未来的资金）;（c）通过研究样本的更大同质性来提高功效。 我们的新受试者（有待未来的项目，以允许基因分型和分析的基础上，在这里收集的主题）将被添加到精神病基因组学联盟的样本，以提高他们的SUD大分析的权力。