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Alcohol Clin Exp Res. 2018 Sep;42(9):1572-1590. doi: 10.1111/acer.13811. Epub 2018 Jul 5.

Genetics of Alcohol Use Disorder: A Role for Induced Pluripotent Stem Cells?

Author information

1
Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
2
Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, New York.
3
Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
4
Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey.

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.

KEYWORDS:

Addiction; Alcohol Use Disorder; Genomewide Association Studies; Human Induced Pluripotent Stem Cells; Neuropsychiatric Disease

PMID:
29897633
PMCID:
PMC6120805
[Available on 2019-09-01]
DOI:
10.1111/acer.13811

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