title: A genome-wide association study of suicidal behavior.
abstract: Genome wide array studies have reported limited success in identifying genetic markers conferring risk for suicidal behavior (SB). This may be attributable to study designs with primary outcome other than SB. We performed a GWAS on suicides and cases with a history of nonfatal suicide attempts compared with psychiatric controls and healthy volunteers. A consortium of USA, Canadian and German teams assembled two groups of cases (suicide attempters and suicides, N = 577) and non-attempter psychiatric and healthy controls (N = 1,233). Logistic regression was used to test genotype-suicidal behavior association. The test was repeated separating suicide attempt and completed suicide as outcomes. No SNP reached genome-wide significance, but several SNPs within STK3, ADAMTS14, PSME2, and TBX20 genes reached P < 1 × 10(-5) . The top SNPs for the suicide attempt analysis included two from DPP10, one from CTNNA3 and one from STK32B. In the suicide analysis we found seven SNPs from the TBX20 gene in the top hits. Pathway analysis identified the following pathways: "Cellular Assembly and Organization," "Nervous System Development and Function," "Cell Death and Survival," "Immunological Disease," "Infectious Disease," and "Inflammatory Response." The top genes in the SB analysis did not overlap with those in the ideation analysis. No genome wide significant results suggest that susceptibility to SB has genetic risk factors with smaller effect sizes. The strongest candidate genes, ADAMTS14, and PSME2 (both linked to inflammatory response), STK3 (neuronal cell death), and TBX20 (brainstem motor neuron development), have not been previously reported in association with suicide and warrant further study.
authors.affiliation: Department of Psychiatry, Columbia University, New York City, New York.|Department of Biostatistics, Columbia University, New York City, New York.
authors.forename: Hanga
authors.initials: H
authors.lastname: Galfalvy
authors.affiliation: Department of Psychiatry, Columbia University, New York City, New York.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Haghighi
authors.affiliation: Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.
authors.forename: Colin
authors.initials: C
authors.lastname: Hodgkinson
authors.affiliation: Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.affiliation: Department of Psychiatry, Columbia University, New York City, New York.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Oquendo
authors.affiliation: Department of Psychiatry, Columbia University, New York City, New York.
authors.forename: Ainsley
authors.initials: A
authors.lastname: Burke
authors.affiliation: Department of Psychiatry, Columbia University, New York City, New York.
authors.forename: Yung-Yu
authors.initials: YY
authors.lastname: Huang
authors.affiliation: Psychiatric Clinic, Martin-Luther-Universität Halle-Wittenberg, Munich, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Giegling
authors.affiliation: Psychiatric Clinic, Martin-Luther-Universität Halle-Wittenberg, Munich, Germany.
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.affiliation: Centre de recherche de l'Institut universitaire en santé mentale de Québec and Département de médecine sociale et préventive, Université Laval, Quebec City, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bureau
authors.affiliation: Department of Psychiatry, McGill University, Montreal, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.affiliation: Department of Psychiatry, Columbia University, New York City, New York.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
mesh_terms: D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005820:Genetic Testing; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D059020:Suicidal Ideation; D013405:Suicide; D013406:Suicide, Attempted; D044465:White People / Q000235:genetics
chemical_list: D005819:Genetic Markers
keywords: GWAS; immune response; suicidal ideation; suicide; suicide attempt