A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder
| Autor: | Peter Propping, Markus M. Nöthen, Amber E. Baum, Winston Corona, Marcella Rietschel, John Hardy, Francis J. McMahon, Sevilla D. Detera-Wadleigh, Jaya M. Satagopan, Cardona I, Susanne Höfels, Alexander Georgi, Thomas G. Schulze, Sven Cichon, R Abou Jamra, Johannes Schumacher, Ben Klemens, Michael Cabanero, Nirmala Akula, M Schwarz |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Linkage disequilibrium Diacylglycerol Kinase Eta Diacylglycerol Kinase Bipolar Disorder Population Genome-wide association study Single-nucleotide polymorphism Biology Models Biological Polymorphism Single Nucleotide Linkage Disequilibrium Article Cellular and Molecular Neuroscience Random Allocation SNP Humans Genetic Predisposition to Disease ANK3 education Molecular Biology Genotyping Genetics education.field_of_study Genome Europe Psychiatry and Mental health Case-Control Studies Female |
| Zdroj: | Molecular psychiatry. 13(2) |
| ISSN: | 1359-4184 |
| Popis: | The genetic basis of bipolar disorder has long been thought to be complex, with the potential involvement of multiple genes, but methods to analyze populations with respect to this complexity have only recently become available. We have carried out a genome-wide association study of bipolar disorder by genotyping over 550,000 single-nucleotide polymorphisms (SNPs) in two independent case-control samples of European origin. The initial association screen was performed using pooled DNA, and selected SNPs were confirmed by individual genotyping. While DNA pooling reduces power to detect genetic associations, there is a substantial cost saving and gain in efficiency. A total of 88 SNPs, representing 80 different genes, met the prior criteria for replication in both samples. Effect sizes were modest: no single SNP of large effect was detected. Of 37 SNPs selected for individual genotyping, the strongest association signal was detected at a marker within the first intron of diacylglycerol kinase eta (DGKH; P=1.5 x 10(-8), experiment-wide P0.01, OR=1.59). This gene encodes DGKH, a key protein in the lithium-sensitive phosphatidyl inositol pathway. This first genome-wide association study of bipolar disorder shows that several genes, each of modest effect, reproducibly influence disease risk. Bipolar disorder may be a polygenic disease. |
| Databáze: | OpenAIRE |
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