Genetics of Alcohol Dependence in African Americans: Recruitment

摘要 美国普遍存在的酒精依赖(AD)在过去十年中大幅增加，对个人和社会都具有极大的破坏性和代价。它也是适度可遗传的。颤动妄想(DTS)是急性酒精戒断的一种常见且往往是危险的后果。我们之前进行了一项AD研究项目，重点关注研究不足的非裔美国人(AA)群体，并进行了大量调查，其中包括一项开创性的全基因组关联研究(GWAS)。我们还报道了许多相关性状的GWAs。我们的发现包括与AD和相关性状相关的全基因组显著(GWS)风险基因座；我们的初步数据支持UNC13C上DTS的风险基因座(P=9.4×10[-9])。许多重要的发现，包括DT协会，仅见于美国儿科学会。 额外招募AA AD受试者并进行最先进的评估是必要的。深入的表型分析将提供其他相关的表型，如危险的性行为。新的招募将建立在我们现有样本的基础上，以增加不仅针对AD，而且针对临床人群中与AD高度共存的其他物质使用障碍(SUD)特征的基因图谱能力。这一资源将有助于对已确定的关联进行复制和更详细、更广泛的调查。对再生障碍性贫血主题的关注将有助于(A)解决这一群体复杂特征研究中公认的差异；(B)使我们能够在观察到我们大多数重要结果的特定人群中跟踪Gwas结果(等待未来的资金)；以及(C)通过研究样本的更大同质性来增加力量。我们的新对象(等待未来的项目，允许基于此处收集的对象进行基因分型和分析)将被添加到精神病学基因组联合会样本中，以提高他们的SUD巨型分析的能力。

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.