Fig. 3
hiPSC models are the bottleneck for molecular validation of hypotheses driven by genome-wide association studies (GWASs). Analyses based on GWASs (n > 100,000 individuals) in combination with clinical investigations allow for definition of causal hypotheses in complex diseases, such as SCZ. The next major step is sufficient patient stratification for the genetic subtype and corresponding subphenotype (n > 100). Subsequent iPSC reprogramming from the identified representative patients remains the bottleneck because the process is so cost and labour intensive. hiPSC models enable experimental validation and evaluation of GWAS-driven hypotheses. These patient-derived cell systems allow researchers to screen treatment options and pave the way for new therapies that can be introduced after being verified in clinical studies with increasing numbers of patients; these studies are best performed in patient subgroups that align with the initial stratification strategy
