iPSCs also offer a new way to study sporadic diseases (the causes of which have not been identified in patients’ family histories or genetic mutations), which is important as the majority of patients with many diseases have sporadic forms of the disease. For example, in Alzheimer’s disease, 95% of patients fall under the sporadic category. Interestingly, analysis of iPSC-derived nerve cells from patients with sporadic Alzheimer’s disease identified several sporadic cases that exhibited the same phenotypes as familial Alzheimer’s disease with a specific gene mutation54 , which indicated that it may be possible to re-classify the sporadic condition using iPSCs. However, modeling sporadic diseases using iPSCs is generally more difficult than monogenic disorders because the phenotypic changes in such diseases are often thought to be induced by multiple small-effect genetic risk variants, in combination with environmental factors. Although iPSCs derived from patients with such diseases would contain disease-relevant risk variants, using iPSCs to model such diseases is complicated by line-to-line variation in genetic and epigenetic background. Such variation is more problematic for modeling sporadic diseases, because the phenotypes of the sporadic disease iPSC-derived cells are expected to be more subtle than for those derived from monogenic diease iPSCs.
