A genome-wide association study of suicidal behavior

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 compa...

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Veröffentlicht in:American journal of medical genetics. Part B, Neuropsychiatric genetics Neuropsychiatric genetics, 2015-10, Vol.168B (7), p.557-563
Hauptverfasser: Galfalvy, Hanga, Haghighi, Fatemeh, Hodgkinson, Colin, Goldman, David, Oquendo, Maria A., Burke, Ainsley, Huang, Yung-yu, Giegling, Ina, Rujescu, Dan, Bureau, Alexandre, Turecki, Gustavo, Mann, J. John
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container_issue 7
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container_title American journal of medical genetics. Part B, Neuropsychiatric genetics
container_volume 168B
creator Galfalvy, Hanga
Haghighi, Fatemeh
Hodgkinson, Colin
Goldman, David
Oquendo, Maria A.
Burke, Ainsley
Huang, Yung-yu
Giegling, Ina
Rujescu, Dan
Bureau, Alexandre
Turecki, Gustavo
Mann, J. John
description 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 
doi_str_mv 10.1002/ajmg.b.32330
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No SNP reached genome‐wide significance, but several SNPs within STK3, ADAMTS14, PSME2, and TBX20 genes reached P &lt; 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. © 2015 Wiley Periodicals, Inc.</description><identifier>ISSN: 1552-4841</identifier><identifier>EISSN: 1552-485X</identifier><identifier>DOI: 10.1002/ajmg.b.32330</identifier><identifier>PMID: 26079190</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Case-Control Studies ; Depressive Disorder, Major - genetics ; Female ; Genetic Markers - genetics ; Genetic Testing ; Genetics ; Genome-Wide Association Study - methods ; GWAS ; Humans ; immune response ; Male ; Mental Disorders - genetics ; Polymorphism, Single Nucleotide ; Risk Factors ; Suicidal Ideation ; Suicide ; suicide attempt ; Suicide, Attempted ; White People - genetics</subject><ispartof>American journal of medical genetics. 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John</creatorcontrib><title>A genome-wide association study of suicidal behavior</title><title>American journal of medical genetics. Part B, Neuropsychiatric genetics</title><addtitle>Am. J. Med. Genet</addtitle><description>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 &lt; 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. © 2015 Wiley Periodicals, Inc.</description><subject>Case-Control Studies</subject><subject>Depressive Disorder, Major - genetics</subject><subject>Female</subject><subject>Genetic Markers - genetics</subject><subject>Genetic Testing</subject><subject>Genetics</subject><subject>Genome-Wide Association Study - methods</subject><subject>GWAS</subject><subject>Humans</subject><subject>immune response</subject><subject>Male</subject><subject>Mental Disorders - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk Factors</subject><subject>Suicidal Ideation</subject><subject>Suicide</subject><subject>suicide attempt</subject><subject>Suicide, Attempted</subject><subject>White People - genetics</subject><issn>1552-4841</issn><issn>1552-485X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0LtPwzAQBnALgXgUNmYUiYWBFJ_txO5YXgVEQUJFsFmOY4NLUkPcAP3vSZ8DA2K6G373SfchtA-4DRiTEzUsX9pZmxJK8RrahiQhMRPJ8_pqZ7CFdkIYYkxxwvkm2iIp5h3o4G3EutGLGfnSxF8uN5EKwWunxs6PojCu80nkbRRqp12uiigzr-rT-WoXbVhVBLO3mC30eHkxOLuKb-9712fd21gnHHAsOpRaS9NMMMMynecZY4pY4MIqw3OWg7Y6VRRzqpRKmCBKELAZGG0hTQhtoaN57nvlP2oTxrJ0QZuiUCPj6yCBEwJpykH8gwLuCCoYa-jhLzr0dTVqHpkpYILitFHHc6UrH0JlrHyvXKmqiQQsp8XLafEyk7PiG36wCK2z0uQrvGy6AWwOvlxhJn-Gye5Nv3e6zI3nZy6MzffqTFVvMuWUJ_LpricHrC8ebgaX8pz-AFe5nJc</recordid><startdate>201510</startdate><enddate>201510</enddate><creator>Galfalvy, Hanga</creator><creator>Haghighi, Fatemeh</creator><creator>Hodgkinson, Colin</creator><creator>Goldman, David</creator><creator>Oquendo, Maria A.</creator><creator>Burke, Ainsley</creator><creator>Huang, Yung-yu</creator><creator>Giegling, Ina</creator><creator>Rujescu, Dan</creator><creator>Bureau, Alexandre</creator><creator>Turecki, Gustavo</creator><creator>Mann, J. 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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. © 2015 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>26079190</pmid><doi>10.1002/ajmg.b.32330</doi><tpages>7</tpages></addata></record>
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subjects Case-Control Studies
Depressive Disorder, Major - genetics
Female
Genetic Markers - genetics
Genetic Testing
Genetics
Genome-Wide Association Study - methods
GWAS
Humans
immune response
Male
Mental Disorders - genetics
Polymorphism, Single Nucleotide
Risk Factors
Suicidal Ideation
Suicide
suicide attempt
Suicide, Attempted
White People - genetics
title A genome-wide association study of suicidal behavior
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