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

Alcohol Clin Exp Res 2018 09 5;42(9):1572-1590. Epub 2018 Jul 5.

Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1111/acer.13811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120805PMC
September 2018
3 Reads

Publication Analysis

Top Keywords

induced pluripotent
8
genes identified
8
alcohol disorder
8
pluripotent stem
8
noncoding regions
8
hipscs derived
4
derived patients
4
patients provide
4
provide powerful
4
cells hipscs
4
human induced
4
cells
4
stem cells
4
powerful platform
4
platform evaluating
4
gwas modeling
4
modeling complex
4
complex interactions
4
identified gwas
4
evaluating genes
4

Similar Publications