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Mol Psychiatry. 2012 Apr;17(4):433-44. doi: 10.1038/mp.2011.4. Epub 2011 Mar 22.

A genome-wide association study of attempted suicide.

Collaborators (192)

Kelsoe JR, Greenwood TA, Barret TB, Nievergelt CM, McKinney R, Shilling D, Schork N, Smith EN, Bloss CS, Nurnberger JI Jr, Edenberg HJ, Foroud T, Koller DM, Gershon E, Liu C, Badner JA, Scheftner WA, Lawson WB, Nwulia EA, Hipolito M, Coryell W, Rice J, Byerley W, McMahon F, Schulze TG, Berrettini W, Potash JB, Zandi PP, Mahon PB, McInnis MG, Zöllner S, Zhang P, Craig D, Szelinger S, Nurnberger J, Miller M, Bowman E, Reich T, Goate A, Rice J, DePaulo R Jr, Simpson S, Stine C, Gershon E, Kazuba D, Maxwell E, Nurnberger J, Miller MJ, Bowman ES, Rau NL, Moe PR, Samavedy N, El-Mallakh R, Manji H, Glitz A, Meyer ET, Flury L, Dick DM, Edenberg H, Rice J, Reich T, Goate A, Bierut L, DePaulo R Jr, MacKinnon DF, Potash JB, Zandi PP, Payne J, Berrettini W, Byerley W, Vawter M, Coryell W, Badner J, McMahon F, Liu C, Sanders A, Caserta M, Harakal D, Scheftner W, Kravitz HM, Marta D, Vaughn-Brown A, McMahon FJ, Kassem L, Murphy DL, Nurnberger J, Miller MJ, Bowman ES, Rau NL, Moe PR, Samavedy N, El Mallakh R, Manji H, Glitz DA, Meyer ET, Smiley C, Foroud T, Flury L, Dick DM, Edenberg H, Rice J, Reich T, Bierut L, McInnis M, DePaulo R, MacKinnon DF, Mondimore FM, Potash JB, Zandi PP, Avramopoulos D, Payne J, Berrottini W, Byerley W, Vawter M, Coryell W, Crowe R, Gershon E, Badner J, McMahon F, Liu C, Sanders A, Caserta M, Dinwiddie S, Nguyen T, Harakal D, Kelsoe J, McKinney R, Scheftner W, Kravitz HM, Marta D, Vaughn-Brown A, Bederow L, McMahon FJ, Kassem L, Detera-Wadleigh S, Austin L, Murphy DL, Nurnberger J, Miller MJ, Bowman ES, Rau NL, Moe PR, Samavedy N, El-Mallakh R, Manji H, Glitz DA, Meyer ET, Smiley C, Foroud T, Flury L, Dick DM, Edenberg H, Rice J, Reich T, Goate A, Bierut L, McInnis M, DePaulo JR Jr, MacKinnon DF, Mondimore FM, Potash JB, Zandi PP, Avramopoulos D, Payne J, Berrettini W, Byerley W, Vinogradov S, Coryell W, Crowe R, Gershon E, Badner J, McMahon F, Liu C, Sanders A, Caserta M, Dinwiddie S, Nguyen T, Harakal D, Kelsoe J, McKinney R, Scheftner W, Kravitz HM, Marta D, Vaughn-Brown A, Bederow L, McMahon FJ, Kassem L, Detera-Wadleigh S, Austin L, Murphy DL, Lawson EN, Hipolito M.

Author information

1
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA. willour@jhmi.edu

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<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 (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.

PMID:
21423239
PMCID:
PMC4021719
DOI:
10.1038/mp.2011.4
[Indexed for MEDLINE]
Free PMC Article

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