The Role of Genetics in Bipolar Disorder

Bipolar disorder is a mental health condition that is believed to be caused by a combination of genetic and environmental factors. Research has shown that bipolar disorder has a strong genetic component, with heritability estimated between 60 and 85% by twin studies. The underlying genetic architecture of bipolar disorder is complex and influenced by a number of genetic variants, each with small effect size, and environmental exposures. Genome-wide association studies (GWAS) have provided meaningful insights into the genetics of bipolar disorder, including replicated genetic variants, and allowed the development of novel multi-marker methods for gene/pathway analysis and for estimating the genetic overlap between bipolar disorder and other traits. However, the existing GWAS had also relevant limitations, such as insufficient statistical power and lack of consideration of rare variants, which may be responsible for the relatively low heritability explained compared to twin studies. The availability of data from large biobanks and automated phenotyping from electronic health records or digital phenotyping represent key steps for providing samples with adequate power for genetic analysis. Next-generation sequencing is becoming more and more feasible in terms of costs, leading to the rapid growth in the number of samples with whole-genome or whole-exome sequence data. These recent and unprecedented resources are of key importance for a more comprehensive understanding of the specific genetic factors involved in bipolar disorder and their mechanistic action in determining disease onset and prognosis. Further research is needed to better understand the specific genetic factors involved and how they interact with environmental factors to cause bipolar disorder.

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