Genetics in psychiatry: Methods, clinical applications and future perspectives.

Psychiatric disorders and related traits have a demonstrated genetic component, with heritability estimated by twin studies generally between 80% and 40%. Their pathogenesis is complex and multi-determined: environmental factors interact with a polygenic architecture, making difficult the development of models able to stratify patients or predict mental health outcomes. Despite this difficult challenge, relevant progress has been made in the field of psychiatric genetics in recent years. This review aims to present the main current methods in psychiatric genetics, their output, limitations, clinical applications, and possible future developments. Genome-wide association studies (GWASs) performed in increasingly large samples have led to the identification of replicated genetic loci associated with the risk of major psychiatric disorders, including schizophrenia and mood disorders. Statistical and biological approaches have been developed to improve our understanding of the etiopathogenetic mechanisms behind genome-wide significant associations, as well as for estimating the cumulative effect of risk variants at the individual level and the genetic overlap between different disorders, as pleiotropy is the rule rather than the exception. Clinical applications are available in the pharmacogenetics field. The main issues that remain to be addressed include improving ethnic diversity in genetic studies and the optimization of statistical power through methodological improvements, such as the definition of dimensional phenotypes with specific biological correlates and the integration of different types of omics data.