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| Title: A genome-wide association study of attempted suicide .
| | Author: Willour VL Seifuddin F Mahon PB Jancic D Pirooznia M Steele J Schweizer B Goes FS Mondimore FM Mackinnon DF Perlis RH Lee PH Huang J Kelsoe JR Shilling PD Rietschel M Nothen M Cichon S Gurling H Purcell S Smoller JW Craddock N DePaulo JR Jr Schulze TG McMahon FJ Zandi PP Potash JB | | Journal: Mol Psychiatry Citation: V : 17 P : 433-44 Year: 2012 Type: MEDLINE | | Literature: oryza Field: abstract Doc ID: pub21423239 Accession (PMID): 21423239 | | 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 x 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 .
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[ Sen. 8, subscore: 2.00 ]: 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 .
[ Sen. 7, subscore: 1.00 ]: 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 .
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