A polygenic trickle of rare disruptive variants in schizophrenia

Polygenic. Schizophrenia is a complex neurodevelopmental disorder that is assumed to be caused by a mixture of genetic and non-genetic factors. The genetic component in schizophrenia is thought to be polygenic, i.e. due to the interaction of multiple genetic factors. Rare variants may play a particular role in this presumable polygenic genetic architecture, but so far this component of the genetic morbidity has been hard to pin down. Now, a recent study in Nature explores the role of rare, disruptive mutations in schizophrenia using large-scale population-based exome sequencing. Let’s find out about a new level of exome-wide honesty and why even a gene with 10 disruptive mutations in cases and none in controls is only mentioned in passing. Continue reading