Gupta Ishaan, Dandavate Rohan, Gupta Pallavi, Agrawal Viplav, Kapoor Manav
Indian Institute of Technology, Delhi, India.
Indian Institute of Science Education and Research, Bhopal, India.
Curr Genet Med Rep. 2020 Jun;8(2):27-34. doi: 10.1007/s40142-020-00185-9. Epub 2020 Mar 17.
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.
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.
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.
酒精使用障碍（AUD）是一种具有很高遗传性的复杂遗传疾病。这种多基因疾病不仅会导致发病率和死亡率增加，还会给家庭和国家带来巨大的社会和经济负担。在过去三十年里，开展了多项基因研究以确定与AUD相关的基因和途径。本综述旨在总结AUD及相关性状基因关联研究的既往工作和最新进展。
最初的基因关联研究取得的成功有限，且由于样本量小而效能较低。AUD是一种多基因性状，需要数千人的数据才能识别效应量较小的遗传因素。随着技术进步以及全基因组关联分析（GWAS）成本的大幅降低，这种情况最近发生了变化。这使得研究人员能够在大型生物样本库和队列中生成基因组数据，并获取广泛的临床和非临床表型。生物样本库数据的公开获取以及研究人员的合作努力，导致发现了几个与AUD及相关性状相关的新位点。目前正在努力确定GWAS位点下的因果变异，以识别AUD潜在的靶基因和生物学机制。许多GWAS变异发生在基因的启动子或增强子区域，并参与因果基因的基因表达调控。此外，来自“ENCODE”、路线图和GTEx等项目的大量“组学”数据也在帮助研究人员整合“多组学”数据，以解释GWAS变异的功能意义。
通过本综述，我们旨在介绍AUD基因和分子研究的最新进展。AUD基因研究的近期成功无疑将激励研究人员，并为这种复杂疾病带来更好的治疗干预措施。
