A number of issues inherent to modeling complex, polygenic diseases with patient-derived stem cells complicate the unambiguous association of in vitro phenotypes with disease pathogenesis. Most notably, given the complex genetic architecture, potential genetic diversity of each individual cell line, and also the technical variability in the isolation of iPSC lines, the studies performed to date, including those described here, have all been underpowered to rigorously test hypotheses about disease etiology and the relationship of specific genetic variants to cellular phenotypes.
