title: A genome-wide association study of attempted suicide.
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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA. willour@jhmi.edu
authors.forename: V L
authors.initials: VL
authors.lastname: Willour
authors.forename: F
authors.initials: F
authors.lastname: Seifuddin
authors.forename: P B
authors.initials: PB
authors.lastname: Mahon
authors.forename: D
authors.initials: D
authors.lastname: Jancic
authors.forename: M
authors.initials: M
authors.lastname: Pirooznia
authors.forename: J
authors.initials: J
authors.lastname: Steele
authors.forename: B
authors.initials: B
authors.lastname: Schweizer
authors.forename: F S
authors.initials: FS
authors.lastname: Goes
authors.forename: F M
authors.initials: FM
authors.lastname: Mondimore
authors.forename: D F
authors.initials: DF
authors.lastname: Mackinnon
authors.forename: R H
authors.initials: RH
authors.lastname: Perlis
authors.forename: P H
authors.initials: PH
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: J R
authors.initials: JR
authors.lastname: Kelsoe
authors.forename: P D
authors.initials: PD
authors.lastname: Shilling
authors.forename: M
authors.initials: M
authors.lastname: Rietschel
authors.forename: M
authors.initials: M
authors.lastname: Nöthen
authors.forename: S
authors.initials: S
authors.lastname: Cichon
authors.forename: H
authors.initials: H
authors.lastname: Gurling
authors.forename: S
authors.initials: S
authors.lastname: Purcell
authors.forename: J W
authors.initials: JW
authors.lastname: Smoller
authors.forename: N
authors.initials: N
authors.lastname: Craddock
authors.forename: J R
authors.initials: JR
authors.lastname: DePaulo
authors.forename: T G
authors.initials: TG
authors.lastname: Schulze
authors.forename: F J
authors.initials: FJ
authors.lastname: McMahon
authors.forename: P P
authors.initials: PP
authors.lastname: Zandi
authors.forename: J B
authors.initials: JB
authors.lastname: Potash
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology*; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods / Q000706:statistics & numerical data*; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D013406:Suicide, Attempted / Q000523:psychology*
chemical_list: D011518:Proto-Oncogene Proteins; C490429:ACP1 protein, human; D017027:Protein Tyrosine Phosphatases