What have we learned from the Psychiatric Genomics Consortium.

Abstract

Decades of research in the pre-molecular genetics era firmly established that major psychiatric disorders are highly to moderately heritable, but only with the emergence of molecular genetic technology about 35 years ago was it possible to envisage identifying the specific pathogenic genes responsible. In psychiatry, the opportunity to probe pathophysiology using DNA seemed particularly attractive given that other biomedical approaches had been frustrated by the complexity of the brain, the challenges in obtaining access to fresh tissue, and the extensive potential for reverse causal associations due to the many environmental and behavioural consequences of the disorders. Simple in concept, translating heritability to pathophysiology has proven arduous. This paper provides a perspective on that process, how some of the obstacles have been overcome, and some of the implications of the current findings. The focus is the work of the Psychiatric Genomics Consortium (PGC), whose main impacts relate to common rather than rare genetic variation. This reflects the data available rather than any ideological position that rare genetic variation is unimportant in psychiatry.