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Genetics of Bipolar Disorder

Susanne Bengesser and Eva Reininghaus

The high hereditary factor of Bipolar Disorder has been proven by many twin-, adoption- and family-studies already decades ago. Concordance rates between monozygotic twins are even as high as 40-70%. Children of two affected parents have a lifetime-risk of 50-65% to fall ill with Bipolar Disorder, while children with one affected parent show a risk of 25% to get Bipolar Disorder. Therefore psychiatric genetics is highly important to detect the genetic blueprint of Bipolar Disorder to invent prevention strategies, as well as individualized pharmacotherapy and new medication targets. Interestingly top susceptibility genes belong to the ion channel group, growth hormones, clock genes, neurotransmitter systems, Lithium sensitive pathway and other important groups. A detailed and exciting description is given by the authors within this book. Furthermore basic principles of genetics, gene-environment-interactions and genetic overlaps between psychiatric diseases are described to picture the whole painting of Genetics of Bipolar Disorder.


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3. Genetics of Bipolar Disorder


3.1 Heritability of Bipolar Disorder Bipolar disorder is a highly heritable disease, which has been proven by many twin and adoption studies for decades. Heritability is as high as 80-85% [Cardno et al. 1999; McGuffin 2003]. Concordance rates between monozygotic twins are 40- 70% and 5-10% for dizygotic twins. The children of two affected parents have a lifetime-risk of 50-65% to fall ill with bipolar disorder, while children with one parent with bipolar disorder only show a risk of 25% to get bipolar disorder. If one first-degree relative suffers from bipolar disorder, one has the risk of 5-10% to develop bipolar disorder. In contrast people without related affected individu- als show a risk of 1% [Rothenhäusler et al. 2004]. This assumes that the genetic constitution is very important for development of manic-depressive disease, but not the only cause. Genetic and environmental factors are the most probable reasons for the pathogenesis of bipolar disorder [Kieseppä et al. 2004]. 3.2 Candidate Genes at One View Since the main model of affective disorders has been dominated by the “neuro- transmitter imbalance theory” for decades, it is not surprising that many highly in- vestigated candidate genes have belonged to neurotransmitter systems (serotoner- gic, noradrenergic, dopaminergic, GABAergic and glutamatergic system) and biogenic amine modulation (e.g. genes encoding for Monoamine-oxidase-A (MAOA), Catechol-O-methyltransferase (COMT) and the Typtophan Hydroxylase 1 (TPH1)). Circadian rhythms are often disturbed in bipolar disorder, so “Clock genes” have been hot spots of research likewise. The growth hormones are another promising chapter of...

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