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dc.contributor.authorDick, Danielle M
dc.contributor.authorMeyers, Jacquelyn
dc.contributor.authorAliev, Fazil
dc.contributor.authorNurnberger, John
dc.contributor.authorKramer, John
dc.contributor.authorKuperman, Sam
dc.contributor.authorPorjesz, Bernice
dc.contributor.authorTischfield, Jay
dc.contributor.authorEdenberg, Howard J
dc.contributor.authorForoud, Tatiana
dc.contributor.authorSchuckit, Marc
dc.contributor.authorGoate, Alison
dc.contributor.authorHesselbrock, Victor
dc.contributor.authorBierut, Laura
dc.date.accessioned2023-02-01T20:06:09Z
dc.date.available2023-02-01T20:06:09Z
dc.identifier.citationDick DM, Meyers J, Aliev F, Nurnberger J Jr, Kramer J, Kuperman S, Porjesz B, Tischfield J, Edenberg HJ, Foroud T, Schuckit M, Goate A, Hesselbrock V, Bierut L. Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts. Am J Med Genet B Neuropsychiatr Genet. 2010 Sep;153B(6):1179-88. doi: 10.1002/ajmg.b.31089. PMID: 20468071; PMCID: PMC3597340.en_US
dc.identifier.eissn1552-485X
dc.identifier.doi10.1002/ajmg.b.31089
dc.identifier.pmid20468071
dc.identifier.urihttp://hdl.handle.net/20.500.12648/8206
dc.description.abstractTwin studies provide strong evidence that there is a shared genetic liability that predisposes to a number of different psychiatric outcomes related to behavioral disinhibition. Further, alcohol dependence comorbid with other disinhibitory disorders is particularly heritable. Chromosome 2p14-2q14.3 has been linked to multiple psychiatric conditions related to behavioral undercontrol. In the Collaborative Study on the Genetics of Alcoholism (COGA), we previously reported linkage to this region with alcohol dependence (AD), suicide attempts (SUI), and conduct disorder (CD). In this study, we follow-up on these previous reports of linkage by combining the phenotypes in analyses that jointly consider the presence of multiple conditions. Linkage analyses of the combined phenotype of AD with CD or SUI results in a maximum LOD score of 5.4 in this region. In addition to this primary linkage peak, independent samples have reported linkage to other alcohol-related phenotypes across chromosome 2. Accordingly, we followed-up these linkage signals by testing for association with SNPs across chromosome 2 in a case-control sample, in which a subset of the cases consisted of alcohol-dependent probands from the linkage sample. We find evidence of association with the combined AD with CD or SUI phenotype, with 23 genes surviving permutation testing. The number of associated genes across the chromosome may explain the persistent linkage findings reported on chromosome 2 across a number of independent studies of alcohol and disinhibitory phenotypes. Further, none of the genes were located directly under the primary COGA linkage peak, which has implications for association tests following-up linkage peaks.
dc.language.isoenen_US
dc.relation.urlhttps://onlinelibrary.wiley.com/doi/10.1002/ajmg.b.31089en_US
dc.rights(c) 2010 Wiley-Liss, Inc.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleEvidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts.en_US
dc.typeArticle/Reviewen_US
dc.source.journaltitleAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Geneticsen_US
dc.source.volume153B
dc.source.issue6
dc.source.beginpage1179
dc.source.endpage88
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.description.versionAMen_US
refterms.dateFOA2023-02-01T20:06:09Z
html.description.abstractTwin studies provide strong evidence that there is a shared genetic liability that predisposes to a number of different psychiatric outcomes related to behavioral disinhibition. Further, alcohol dependence comorbid with other disinhibitory disorders is particularly heritable. Chromosome 2p14-2q14.3 has been linked to multiple psychiatric conditions related to behavioral undercontrol. In the Collaborative Study on the Genetics of Alcoholism (COGA), we previously reported linkage to this region with alcohol dependence (AD), suicide attempts (SUI), and conduct disorder (CD). In this study, we follow-up on these previous reports of linkage by combining the phenotypes in analyses that jointly consider the presence of multiple conditions. Linkage analyses of the combined phenotype of AD with CD or SUI results in a maximum LOD score of 5.4 in this region. In addition to this primary linkage peak, independent samples have reported linkage to other alcohol-related phenotypes across chromosome 2. Accordingly, we followed-up these linkage signals by testing for association with SNPs across chromosome 2 in a case-control sample, in which a subset of the cases consisted of alcohol-dependent probands from the linkage sample. We find evidence of association with the combined AD with CD or SUI phenotype, with 23 genes surviving permutation testing. The number of associated genes across the chromosome may explain the persistent linkage findings reported on chromosome 2 across a number of independent studies of alcohol and disinhibitory phenotypes. Further, none of the genes were located directly under the primary COGA linkage peak, which has implications for association tests following-up linkage peaks.
dc.description.institutionSUNY Downstateen_US
dc.description.departmentHenri Begleiter Neurodynamics Laboratoryen_US
dc.description.degreelevelN/Aen_US
dc.identifier.journalAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics


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