Genetics of Psychiatric Disorders: Advances in Genetic Epidemiology and Genomic Approaches

The heritability of psychiatric disorders is well established, and there is growing elucidation of their molecular genetic architecture. This chapter reviews evidence from genetic epidemiological studies, exemplified by family, twin, and adoption studies that document the role of genetic factors in psychiatric disorders and research on their molecular basis ranging from genetic linkage and candidate gene association studies, and genome-wide association studies, to the current era of whole-genome sequencing. By familiarizing the reader with the concepts of common and rare genetic variations and polygenicity as hallmarks of genetically complex psychiatric disorders, it is depicted how genetic research into mental illness has evolved from merely trying to identify risk genes to understanding the complete, i.e., genomic picture of how a multitude of variants contribute to overall phenotypic variability. Sources of complexity including epistasis (gene-gene interactions) and environmental factors that may influence gene expression are described. The results from large-scale global collaborations that have yielded several hundred genetic variants involved in schizophrenia, bipolar disorder, major depression, and anxiety and substance use disorders are presented. In particular, the application of these findings are emphasized to achieve the ultimate goal of psychiatric genetics aid in prevention, diagnosis, therapy, and prognosis, through application of polygenic profile scores, psychiatric pharmacogenetics as a precision medicine tool, and hands-on genetic counseling. A way forward is outlined, which includes stringent biobanking, the definition of novel phenotypes, and population-based research. Work remains in psychiatric genetic research, and this chapter helps the reader discover how identifying relevant molecular pathways and functional mechanisms may help to improve the understanding of the pathophysiology of mental illness and identify targets for drug repurposing, or even entirely new drug targets.