EXAMINING THE SHARED ETIOLOGY OF PSYCHOPATHOLOGY WITH GENOME-WIDE ASSOCIATION STUDIES

Genome-wide association studies (GWASs) have ushered in a new era of reproducible discovery in psychiatric genetics. The field has now identified hundreds of common genetic variants that are associated with mental dis-orders, and many of them influence more than one disorder. By advancing the understanding of causal biology underlying psychopathology, GWAS results are poised to inform the development of novel therapeutics, stratifi- cation of at-risk patients, and perhaps even the revision of top-down classification systems in psychiatry. Here, we provide a concise review of GWAS findings with an emphasis on findings that have elucidated the shared genetic etiology of psychopathology, summarizing insights at three levels of analysis: 1) genome-wide architecture; 2) networks, pathways, and gene sets; and 3) individual variants/genes. Three themes emerge from these efforts. First, all psychiatric phenotypes are heritable, highly polygenic, and influenced by many pleiotropic variants with incomplete penetrance. Second, GWAS results highlight the broad etiological roles of neuronal biology, system-wide effects over localized effects, and early neurodevelopment as a critical period. Third, many loci that are robustly associated with multiple forms of psychopathology harbor genes that are involved in synaptic structure and function. Finally, we conclude our review by discussing the implications that GWAS results hold for the field of psychiatry, as well as expected challenges and future directions in the next stage of psychiatric genetics.

Automated summary

Genome-wide association studies have led to reproducible discoveries in psychiatric genetics, identifying hundreds of common genetic variants associated with mental disorders. These findings have the potential to inform the development of new therapeutics, stratify at-risk patients, and possibly revise classification systems in psychiatry. The review summarizes GWAS findings at three levels of analysis: genome-wide architecture, networks and pathways, and individual variants/genes. Three themes emerge: heritability and polygenic nature of psychiatric phenotypes, the importance of neuronal biology and early neurodevelopment, and the involvement of synaptic structure and function in psychopathology. The implications of GWAS results for psychiatry and future directions are also discussed.