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Genetics of Alcohol Use Disorder: A Role for Induced Pluripotent Stem Cells?
Author(s) -
Prytkova Iya,
Goate Alison,
Hart Ronald P.,
Slesinger Paul A.
Publication year - 2018
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13811
Subject(s) - genome wide association study , induced pluripotent stem cell , genome editing , biology , phenotype , genome , computational biology , disease , genetic association , human induced pluripotent stem cells , gene , heritability , genetics , neuroscience , medicine , single nucleotide polymorphism , embryonic stem cell , genotype , pathology
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. AUD s have a strong heritability, but only a few genes have been identified with a large effect size on disease phenotype. Genomewide association studies ( GWAS s) 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 (hi PSC s) derived from patients provide a powerful platform for evaluating genes identified by GWAS and modeling complex interactions in the human genome. hi PSC s 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 hi PSC ‐derived central nervous system cells for modeling AUD s in addition to highlighting successful applications of hi PSC s in polygenic neuropsychiatric diseases.