Focusing on a genetically defined cohort, a subsequent hiPSC study explored a GABRA2 variant (rs279858*C) (Lieberman et al., 2015) which has been repeatedly associated with AUD (Covault et al., 2004, 2008; Edenberg et al., 2004; Ittiwut et al., 2012; Li et al., 2014). GABRA2 encodes the alpha subunit of the pentameric GABAA receptor, and is located in chromosome 4p12, tandem to three other GABAA subunits. rs279858*C is a synonymous mutation in exon 5, with no effect on protein structure. Other GABAA subunits are located on chromosomes 5q34, 15q11, and Xq28 (Steiger and Russek, 2004). mRNA encoding GABAA subunits on 4p12 as well as subunits located on other chromosomes were measured in 36 neural lines from alcoholic and non-alcoholic donors (Lieberman et al., 2015). Carriers of rs279858*C had significantly lower levels of all GABAA subunits located on 4p12, but not other chromosomal regions (Lieberman et al., 2015). However, protein levels in postmortem cortex did not vary by rs279858 genotype, suggesting the polymorphism’s effects may be most profound during neural development (Lieberman et al., 2015). In a more recent study, 24-hour and
