Abstract

Mental disorders and traits are heritable, but the underlying molecular mechanisms are largely unknown. Recent progress in genetic technology has enabled large scale genome-wide studies with millions of genetic variants analysed in large number of participants. This has led to a series of discoveries of genetic variants associated with mental traits and disorders.

A key feature is the high number of genetic variants each with small effects. For example, there are now 270 loci associated with schizophrenia, 298 loci associated with bipolar disorder, and over 600 loci associated with depression, identified in studies including 2-3 million participants. Such a polygenic architecture seems to be present for many brain-related traits, including measures of brain MRI structure and function. Application of novel analytical tools has revealed distributed effects of many genomic variants across different parts of the brain, suggestion pleiotropic mechanisms. Further, recent functional annotation analyses building on large repositories of molecular aspects of neurons, tissue and brain regions of the human brain with genetic enrichment tools has greatly accelerated our understanding of the underlying neuronal mechanisms, which can be followed up in experimental studies.

I will review the recent findings and focus on the new opportunities for neuroscience insights obtained from the recent large scale genetic studies of mental disorders and traits.