The Current Progress of Psychiatric Genomics.

Psychiatric disorders such as bipolar disorder and schizophrenia are highly heritable. While the genetic contribution to psychiatric disorders is quite sure, specific genetic factors contributing to particular conditions have long been a mystery. Empowered by the initial report of the Human Genome Project, the analysis of the comprehensive set of the human genome, called "genomics," became possible. Subsequent development of large-scale genomic technologies enabled us to elucidate various disease-related genetic information, accelerating our understanding of various diseases. Genomic research on psychiatric disorders is not an exception. In this Review, I introduce significant advancements in psychiatric genomics with a special focus on our investigation of bipolar disorder. International consortiums and advocacy groups accelerate psychiatric genomics, increasing the sample size and statistical power for robust findings. The genetic architecture of schizophrenia has been elucidated in both common and rare variant studies. The genetic architecture of autism spectrum disorder (ASD) has been elucidated mainly by rare variant analysis. As to bipolar disorder, common variant analysis precedes rare variant analysis, but we are struggling to elucidate relevant rare variants. While the genomic approach has explained specific genetic factors for particular disorders, overlapping risk genes or pleiotropy has been observed more than expected. The boundary in the current nosology of psychiatric disorders is more or less challenged. To understand the genotype-phenotype relation more deeply, an attempt to understand phenotypes based on genotypes, called the "genotype first" approach, has started. I discuss this new approach for better understanding and treatment of psychiatric disorders.