To explore molecular effects of AD-associated variants in the GABRA2 haplotype block, we used an induced pluripotent stem cell (iPSC) model system (Takahashi and Yamanaka, 2006, Takahashi et al., 2007). Generation of iPSCs from individuals with known genotypes and subsequent differentiation into neural cells provides an opportunity to explore molecular phenotypes of AD-associated genetic variants in vitro. We examined neural cell cultures differentiated from 36 iPSC lines from 21 donor subjects with different GABRA2 rs279858 genotypes and RNA expression of genes encoding GABAA receptor subunits was examined. Our results indicate that chr4p12 AD risk alleles are associated with differences in RNA expression of all four GABAA genes located in this region in this in vitro model system.
