酒精使用障碍基因研究的最新进展。

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Accounts of Chemical Research Pub Date : 2020-06-01 Epub Date: 2020-03-17 DOI:10.1007/s40142-020-00185-9
Ishaan Gupta, Rohan Dandavate, Pallavi Gupta, Viplav Agrawal, Manav Kapoor
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引用次数: 0

摘要

综述目的:酒精使用障碍(AUD)是一种复杂的遗传性疾病,具有极高的遗传率。这种多基因疾病不仅会增加发病率和死亡率,还会给家庭和国家带来巨大的社会和经济负担。在过去的三十年里,人们开展了多项遗传学研究,以确定与 AUD 相关的基因和途径。本综述旨在总结 AUD 及相关性状遗传关联研究的过去努力和最新进展:最初的遗传关联研究仅取得了有限的成功,但由于样本量较小,研究效率较低。AUD 是一种多基因性状,需要来自数千个个体的数据才能确定影响较小的遗传因素。最近,随着技术的进步和全基因组关联分析(GWAS)成本的大幅降低,情况发生了变化。这使得研究人员能够生成超大型生物库和队列的基因组数据,并获得大量临床和非临床表型。公众对生物库数据的访问和研究人员的共同努力,导致鉴定出与 AUD 和相关性状有关的几个新基因位点。目前正在努力鉴定 GWAS 基因座下的因果变异,以确定目标基因和 AUDs 的生物机制。许多 GWAS 变异发生在基因的启动子或增强子区域,参与调控致病基因的表达。此外,来自 "ENCODE"、RoadMap和GTEx等项目的大量 "组学 "数据也有助于研究人员整合 "多组学 "数据来解释GWAS变异的功能意义。近期在 AUDs 遗传学研究方面取得的成功必将激励研究人员,并为这一复杂疾病带来更好的治疗干预措施。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Recent advances in genetic studies of alcohol use disorders.

Purpose of review: Alcohol use disorder (AUD) is a complex genetic disorder with very high heritability. This polygenic disorder not only results in increased morbidity and mortality, it is also a substantial social and economic burden on families and the nation. For past three decades, several genetic studies were conducted to identify genes and pathways associated with AUD. This review aims to summarize past efforts and recent advances in genetic association studies of AUD and related traits.

Recent findings: Initial genetic association studies achieved a limted success and suffered from low power due to small sample sizes. AUD is a polygenic trait and data from several thousands individuals was required to identify the genetic factors of small effect sizes. The scenario changed recently with technological advances and significant reduction in cost of the genome wide association analyses (GWAS). This enabled researchers to generate genomic data on mega biobanks and cohorts with access to extensive clinical and non-clinical phenotypes. Public access to data from biobanks and collaborative efforts of researchers lead to identification of several novel loci associated with AUDs and related traits. Efforts are now underway to identify the causal variants under the GWAS loci to identify target genes and biological mechanisms underpining AUDs. Many GWAS variants occur in promoter or enhancer regions of the genes and are involved in regulation of gene expression of causal genes. This, large amounts of "omics" data from projects such as "ENCODE", RoadMap and GTEx is also helping researchers to integrate "multi-omics" data to interpret functional significance of GWAS variants.

Summary: With current review, we aim to present the recent advances in genetic and molecular studies of AUDs. Recent successes in genetic studies of AUDs will definetely motivate researchers and lead to better therapeutic interventions for this complex disorder.

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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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