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A genome-wide association study of attempted suicide
The heritable component to attempted and completed suicide is partly related to psychiatric disorders and also partly independent of them. While 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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021719/ https://www.ncbi.nlm.nih.gov/pubmed/21423239 http://dx.doi.org/10.1038/mp.2011.4 |
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author | Willour, Virginia L. Seifuddin, Fayaz Mahon, Pamela B. Jancic, Dubravka Pirooznia, Mehdi Steele, Jo Schweizer, Barbara Goes, Fernando S. Mondimore, Francis M. MacKinnon, Dean F. Perlis, Roy H. Lee, Phil Hyoun Huang, Jie Kelsoe, John R. Shilling, Paul D. Rietschel, Marcella Nöthen, Markus Cichon, Sven Gurling, Hugh Purcell, Shaun Smoller, Jordan W. Craddock, Nicholas DePaulo, J. Raymond Schulze, Thomas G. McMahon, Francis J. Zandi, Peter P. Potash, James B. |
author_facet | Willour, Virginia L. Seifuddin, Fayaz Mahon, Pamela B. Jancic, Dubravka Pirooznia, Mehdi Steele, Jo Schweizer, Barbara Goes, Fernando S. Mondimore, Francis M. MacKinnon, Dean F. Perlis, Roy H. Lee, Phil Hyoun Huang, Jie Kelsoe, John R. Shilling, Paul D. Rietschel, Marcella Nöthen, Markus Cichon, Sven Gurling, Hugh Purcell, Shaun Smoller, Jordan W. Craddock, Nicholas DePaulo, J. Raymond Schulze, Thomas G. McMahon, Francis J. Zandi, Peter P. Potash, James B. |
author_sort | Willour, Virginia L. |
collection | PubMed |
description | The heritable component to attempted and completed suicide is partly related to psychiatric disorders and also partly independent of them. While 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 1,201 bipolar (BP) subjects with a history of suicide attempts to the genotypes of 1,497 BP subjects without a history of suicide attempts. 2,507 SNPs with evidence for association at p<0.001 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 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. |
format | Online Article Text |
id | pubmed-4021719 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
record_format | MEDLINE/PubMed |
spelling | pubmed-40217192014-05-15 A genome-wide association study of attempted suicide Willour, Virginia L. Seifuddin, Fayaz Mahon, Pamela B. Jancic, Dubravka Pirooznia, Mehdi Steele, Jo Schweizer, Barbara Goes, Fernando S. Mondimore, Francis M. MacKinnon, Dean F. Perlis, Roy H. Lee, Phil Hyoun Huang, Jie Kelsoe, John R. Shilling, Paul D. Rietschel, Marcella Nöthen, Markus Cichon, Sven Gurling, Hugh Purcell, Shaun Smoller, Jordan W. Craddock, Nicholas DePaulo, J. Raymond Schulze, Thomas G. McMahon, Francis J. Zandi, Peter P. Potash, James B. Mol Psychiatry Article The heritable component to attempted and completed suicide is partly related to psychiatric disorders and also partly independent of them. While 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 1,201 bipolar (BP) subjects with a history of suicide attempts to the genotypes of 1,497 BP subjects without a history of suicide attempts. 2,507 SNPs with evidence for association at p<0.001 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 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. 2011-03-22 2012-04 /pmc/articles/PMC4021719/ /pubmed/21423239 http://dx.doi.org/10.1038/mp.2011.4 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Willour, Virginia L. Seifuddin, Fayaz Mahon, Pamela B. Jancic, Dubravka Pirooznia, Mehdi Steele, Jo Schweizer, Barbara Goes, Fernando S. Mondimore, Francis M. MacKinnon, Dean F. Perlis, Roy H. Lee, Phil Hyoun Huang, Jie Kelsoe, John R. Shilling, Paul D. Rietschel, Marcella Nöthen, Markus Cichon, Sven Gurling, Hugh Purcell, Shaun Smoller, Jordan W. Craddock, Nicholas DePaulo, J. Raymond Schulze, Thomas G. McMahon, Francis J. Zandi, Peter P. Potash, James B. A genome-wide association study of attempted suicide |
title | A genome-wide association study of attempted suicide |
title_full | A genome-wide association study of attempted suicide |
title_fullStr | A genome-wide association study of attempted suicide |
title_full_unstemmed | A genome-wide association study of attempted suicide |
title_short | A genome-wide association study of attempted suicide |
title_sort | genome-wide association study of attempted suicide |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021719/ https://www.ncbi.nlm.nih.gov/pubmed/21423239 http://dx.doi.org/10.1038/mp.2011.4 |
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