Genetics of Alcohol Use Disorder: A Role for Induced Pluripotent Stem Cells?. (5th July 2018)

• Record Type: Journal Article
• Authors: Prytkova, Iya; Goate, Alison; Hart, Ronald P.; Slesinger, Paul A.
• Is Part Of: Alcoholism. Volume 42:Number 9(2018)
• Page Start: 1572
• Page End: 1590
• Publication Date: 2018-07-05
• Subjects: Alcohol Use Disorder -- Human Induced Pluripotent Stem Cells -- Genomewide Association Studies -- Addiction -- Neuropsychiatric Disease; Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.13811
• Languages: English
• ISSNs: 0145-6008

Abstract

Abstract : Alcohol use disorder (AUD) affects millions of people and costs nearly 250 billion dollars annually. Few effective FDA‐approved treatments exist, and more are needed. AUDs have a strong heritability, but only a few genes have been identified with a large effect size on disease phenotype. Genomewide association studies (GWASs) have identified common variants with low effect sizes, most of which are in noncoding regions of the genome. Animal models frequently fail to recapitulate key molecular features of neuropsychiatric disease due to the polygenic nature of the disease, partial conservation of coding regions, and significant disparity in noncoding regions. By contrast, human induced pluripotent stem cells (hiPSCs) derived from patients provide a powerful platform for evaluating genes identified by GWAS and modeling complex interactions in the human genome. hiPSCs can be differentiated into a wide variety of human cells, including neurons, glia, and hepatic cells, which are compatible with numerous functional assays and genome editing techniques. In this review, we focus on current applications and future directions of patient hiPSC‐derived central nervous system cells for modeling AUDs in addition to highlighting successful applications of hiPSCs in polygenic neuropsychiatric diseases. Abstract : In this critical review we summarize the advances and challenges of genome wide association studies in investigating Alcohol Use Disorders (AUDs), focusing on central nervous system (CNS) contributions to the disorder and how human induced pluripotent stem cells (hiPSCs) can be of utility. We review applications, advantages, and limitations of hiPSC‐derived CNS cells for modeling polygenic neuropsychiatric disease, recent work investigating AUDs with this technology, and future directions for the field of AUD genetics and hiPSCs.