The genetic architecture of bipolar disorder: Entering the road of discoveries

Bipolar disorder is a severe mental disorder characterized by episodes of abnormal mood, including both mania and depression. Accumulation of bipolar disorder in families has been observed for centuries, and genetic epidemiology studies have demonstrated a high degree of heritability. However, it is only in recent years that many disease risk genes have been identified, leveraging genome-wide genotyping technology and large samples from international collaborations, particularly the Psychiatric Genomics Consortium. It is likely that bipolar disorder patients inherit a number of gene variants that increase vulnerability to disease, and are exposed to stress conditions that trigger the disease and cause relapses. The genetic risk loci identified so far explain too little variance to be used for clinical diagnostics or for individual prediction of disease risk. Further, the specific molecular genetic mechanisms underlying susceptibility to bipolar disorder are still poorly understood. However, through large-scale international efforts, we are expecting a series of genetic discoveries in bipolar disorders in the coming years, providing a better understanding of disease mechanisms. This new knowledge will form a basis for developing better pharmacological agents and inform new diagnostic tools, with great potential for personalized medicine approaches in bipolar disorders. In line with the recently improved insight into the genetic architecture of bipolar disorders, it is important to communicate the stress-vulnerability model to patients and relatives, which can promote better acceptance and involvement from patients and the community, leading to better treatment adherence and outcome.