A genome-wide association study of attempted suicide

V. L. Willour, F. Seifuddin, P. B. Mahon, D. Jancic, M. Pirooznia, J. Steele, Barbara W Schweizer, Fernando S Goes, Francis M Mondimore, Dean F Mackinnon, R. H. Perlis, P. H. Lee, J. Huang, J. R. Kelsoe, P. D. Shilling, M. Rietschel, M. Nöthen, S. Cichon, H. Gurling, S. PurcellJ. W. Smoller, N. Craddock, J Raymond Depaulo, T. G. Schulze, F. J. McMahon, Peter P Zandi, James Bennett Potash

Research output: Contribution to journalArticle

Abstract

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 P-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.

Original languageEnglish (US)
Pages (from-to)433-444
Number of pages12
JournalMolecular Psychiatry
Volume17
Issue number4
DOIs
StatePublished - Apr 2012

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Keywords

  • 2p25
  • ACP1
  • lithium
  • LRRTM4
  • Wnt

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Willour, V. L., Seifuddin, F., Mahon, P. B., Jancic, D., Pirooznia, M., Steele, J., Schweizer, B. W., Goes, F. S., Mondimore, F. M., Mackinnon, D. F., Perlis, R. H., Lee, P. H., Huang, J., Kelsoe, J. R., Shilling, P. D., Rietschel, M., Nöthen, M., Cichon, S., Gurling, H., ... Potash, J. B. (2012). A genome-wide association study of attempted suicide. Molecular Psychiatry, 17(4), 433-444. https://doi.org/10.1038/mp.2011.4