Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts

Danielle M. Dick, Jacquelyn Meyers, Fazil Aliev, John Nurnberger, John Kramer, Sam Kuperman, Bernice Porjesz, Jay Tischfield, Howard J. Edenberg, Tatiana Foroud, Marc Schuckit, Alison Goate, Victor Hesselbrock, Laura Bierut

Research output: Contribution to journalArticle

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1179-1188
Number of pages10
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume153
Issue number6
DOIs
StatePublished - Sep 2010

Keywords

  • Alcoholism
  • Association
  • Behavioral disinhibition
  • Genetics
  • Linkage

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Dick, D. M., Meyers, J., Aliev, F., Nurnberger, J., Kramer, J., Kuperman, S., Porjesz, B., Tischfield, J., Edenberg, H. J., Foroud, T., Schuckit, M., Goate, A., Hesselbrock, V., & Bierut, L. (2010). Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 153(6), 1179-1188. https://doi.org/10.1002/ajmg.b.31089