Genetics of Bipolar Spectrum Disorders: Focus on Family Studies Using Whole Exome Sequencing

Family, twin, adoption studies showed that bipolar spectrum disorders—bipolar disorder (BD) types 1 and 2, cyclothymic disorder—may have a familial nature and aggregate among relatives. Moreover, in persons with a history of BD, an earlier manifestation, a more frequent presence of concomitant psychopathology, and a more severe course of the disease are noted. At the same time, despite the high inheritability (up to 85%), BD is phenotypically and genetically very heterogeneous. Modern molecular genetic studies of BD have not shown any convincing results with respect to robust markers of the risk of this disorder. A new solution can be an integrated approach using family design and sequencing methods of the new generation. Studies with a similar methodology have been able to identify new genetic variants associated with BD, which are involved in the development of the cerebral cortex, circadian rhythms, and the processes of glutamate neurotransmission. The family design provides the maximum likelihood of detecting specific genetic markers associated not only with the phenotype but also with potential family forms of BD.