required match, and this is especially true in the case of post-mortem tissue samples, due to the limited availability of covariates-matched tissue samples. The family design can be considered a subclass of the matched pair design, where the family (genetic) background is the controlled factor. It has been extensively used in genomic studies to investigate genetic transmission within families; for example, to discover de novo mutations. It is a powerful approach that was successfully implemented in a recent hiPSCs based autism study 50. This design is not really accessible using post-mortem tissue. The advantage of a family design in the context of hiPSC studies is that it is better suited to a low number of samples in that it allows better control of genetic background effects, which have been shown to drive a large portion of variability across hiPSC lines. A potential drawback may be the intrinsic age difference between probands and controls, when children used as probands are opposed to their parents. Various groups have shown that the “age signature” of the cell donor appears to be reset by the reprogramming process 55,56, while this reversal does not appear to occur when the somatic cell is directly converted into
