A genome-wide association study of attempted suicide
| Autor: | Hugh Gurling, Pamela B. Mahon, Paul D. Shilling, Francis M. Mondimore, Virginia L. Willour, Shaun Purcell, Fayaz Seifuddin, Mehdi Pirooznia, Markus M. Nöthen, Jinyan Huang, Dean F. MacKinnon, Roy H. Perlis, James B. Potash, Jo Steele, Francis J. McMahon, Thomas G. Schulze, Jordan W. Smoller, Marcella Rietschel, J. R. DePaulo, Peter P. Zandi, Nicholas John Craddock, Phil Lee, Dubravka Jancic, John R. Kelsoe, Fernando S. Goes, Barbara W. Schweizer, Sven Cichon |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Linkage disequilibrium Bipolar Disorder Genotype Poison control Genome-wide association study Single-nucleotide polymorphism Suicide Attempted Suicide prevention Polymorphism Single Nucleotide Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Polymorphism (computer science) Proto-Oncogene Proteins Medicine SNP Humans Genetic Predisposition to Disease Molecular Biology 030304 developmental biology Genetics 0303 health sciences business.industry Brain 16. Peace & justice Psychiatry and Mental health Case-Control Studies Female Protein Tyrosine Phosphatases business 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Molecular psychiatry |
| ISSN: | 1476-5578 |
| Popis: | The heritable component to attempted and completed suicide is partly related to psychiatric disorders and also partly independent of them. Although attempted suicide linkage regions have been identified on 2p11-12 and 6q25-26, there are likely many more such loci, the discovery of which will require a much higher resolution approach, such as the genome-wide association study (GWAS). With this in mind, we conducted an attempted suicide GWAS that compared the single-nucleotide polymorphism (SNP) genotypes of 1201 bipolar (BP) subjects with a history of suicide attempts to the genotypes of 1497 BP subjects without a history of suicide attempts. In all, 2507 SNPs with evidence for association at P0.001 were identified. These associated SNPs were subsequently tested for association in a large and independent BP sample set. None of these SNPs were significantly associated in the replication sample after correcting for multiple testing, but the combined analysis of the two sample sets produced an association signal on 2p25 (rs300774) at the threshold of genome-wide significance (P=5.07 × 10(-8)). The associated SNPs on 2p25 fall in a large linkage disequilibrium block containing the ACP1 (acid phosphatase 1) gene, a gene whose expression is significantly elevated in BP subjects who have completed suicide. Furthermore, the ACP1 protein is a tyrosine phosphatase that influences Wnt signaling, a pathway regulated by lithium, making ACP1 a functional candidate for involvement in the phenotype. Larger GWAS sample sets will be required to confirm the signal on 2p25 and to identify additional genetic risk factors increasing susceptibility for attempted suicide. |
| Databáze: | OpenAIRE |
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