Seminar Series

A primer on the genetics of psychiatric disorders

Psychiatric disorders are very highly heritable but their genetics is complex, and, until recently, few specific genes have been known. Recent discoveries have changed that, with many causal genetic variants being identified for disorders like schizophrenia and autism. These include many rare mutations that each individually increase risk substantially, notably cutting across diagnostic boundaries. Common genetic variants have also been discovered, which have much smaller individual effects but which collectively may explain a substantial proportion of risk. I will discuss a model that accommodates both types of genetic risk factor, and explore the implications of the genetic architecture for investigations into the pathophysiology of these conditions. In particular, the underlying etiological heterogeneity presents a confound for studies based on diagnostic categories, but also a means to make progress by focusing instead on patients with similar mutations. Finally, the genes identified are enriched for those involved in neural development, but still have extremely diverse functions. How mutations in so many different genes can result in a characteristic set of convergent phenotypes remains mysterious. I will discuss how this may be explained by the idea of emergent phenotypes and specific failure modes of dynamical systems.