Bipolar disorder (BD) is a common mental disorder characterized by recurrent mood episodes, which causes major socioeconomic burdens globally. Though its disease pathogenesis is largely unknown, the high heritability of BD indicates strong contributions from genetic factors. In this review, we summarize the recent achievements in the genetics of BD, particularly those from genome-wide association study (GWAS) of common variants and next-generation sequencing analysis of rare variants. These include the identification of dozens of robust disease-associated loci, deepening of our understanding of the biology of BD, objective description of correlations with other psychiatric disorders and behavioral traits, formulation of methods for predicting disease risk and drug response, and the discovery of a single gene associated with bipolar disorder and schizophrenia spectrum with a large effect size. On the other hand, the findings to date have not yet made a clear contribution to the improvement of clinical psychiatry of BD. We overview the remaining challenges as well as possible paths to resolve them, referring to studies of other major neuropsychiatric disorders.
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This work was in part supported by grants from the Japan Agency for Medical Research and Development (AMED) under Grant Number JP21km0405214 (to A.T.) and JSPS KAKENHI under Grant Numbers JP20H05777 (to A.T.), 21H02855 (to A.T.) and 20KK0225 (to Y.O). This study was also supported by the RIKEN Junior Research Associate Program (to T.H.).
The authors declare no competing interests.
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Hara, T., Owada, Y. & Takata, A. Genetics of bipolar disorder: insights into its complex architecture and biology from common and rare variants. J Hum Genet 68, 183–191 (2023). https://doi.org/10.1038/s10038-022-01046-9