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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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5. Gene-environment-interactions and prevention


5.1 Epigenetics Lifestyle and environmental factors, including diet, drugs, alcohol and hormones, can influence inherited features without changing DNA sequence, however, with epigenetic changes, including methylation, acetylation, ubiquitination and phos- phorylation of DNA or histones. Thus environment has an impact on inheritability and gene regulation with chemical modification of DNA segments (e.g. promo- ters), which are important for gene expression. Especially cytosine in so-called CpG islands, which are located especially in regulatory elements, gets methy- lated. The methyl group is provided by S-adenosyl methionine. Hypermethyla- tion of promoters lead to silencing of the gene or reduced transcription, irreversi- ble if very densely methylated [Bogdanovic et al. 2009]. Potentially all genes of our genome could be expressed in every cell, because every cell carries the whole genome inside. However, since cells are specialized and adaption to envi- ronment is important, not all genes are necessary and some must be silenced. This happens along with other mechanisms by epigenetic modification. Those chemical changes are performed by many host enzymes. DNA methyltransferases are re- sponsible for DNA methylation, and histones are modified by histone acetyl- transferases (HATs), histone deacetylases (HDACs), as well as methyl- transferases and demethylases [Abdolmaleky et al. 2004; Connor et al. 2008]. Many neurodevelopmental and neuropsychiatric diseases, including Prader Willi und Angelman syndrome, are influenced by epigenetic changes and genomic imprinting [Horstthemke et al. 2008]. Epigenetic changes, for example patholog- ical increased CpG methylation and repressive chromatin remodeling at 5’ regu- latory sequences, might also be a cause for heritable...

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