title: Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts.
abstract: Twin 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.
authors.affiliation: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298-0126, USA. ddick@vcu.edu
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Dick
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Meyers
authors.forename: Fazil
authors.initials: F
authors.lastname: Aliev
authors.forename: John
authors.initials: J
authors.lastname: Nurnberger
authors.forename: John
authors.initials: J
authors.lastname: Kramer
authors.forename: Sam
authors.initials: S
authors.lastname: Kuperman
authors.forename: Bernice
authors.initials: B
authors.lastname: Porjesz
authors.forename: Jay
authors.initials: J
authors.lastname: Tischfield
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.forename: Marc
authors.initials: M
authors.lastname: Schuckit
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
authors.forename: Victor
authors.initials: V
authors.lastname: Hesselbrock
authors.forename: Laura
authors.initials: L
authors.lastname: Bierut
mesh_terms: D000437:Alcoholism / Q000150:complications / Q000235:genetics*; D016022:Case-Control Studies; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D019955:Conduct Disorder / Q000235:genetics*; D056726:Genetic Association Studies; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats / Q000235:genetics; D010641:Phenotype; D013406:Suicide, Attempted
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