Journal article
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, Vol.153B(6), pp.1179-1188
09/2010
DOI: 10.1002/ajmg.b.31089
PMCID: PMC3597340
PMID: 20468071
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.
Details
- Title: Subtitle
- Evidence for Genes on Chromosome 2 Contributing to Alcohol Dependence With Conduct Disorder and Suicide Attempts
- Creators
- Danielle M Dick - University of Connecticut Health Center, Farmington, ConnecticutJacquelyn Meyers - University of Connecticut Health Center, Farmington, ConnecticutFazil Aliev - University of Connecticut Health Center, Farmington, ConnecticutJohn Nurnberger - University of Connecticut Health Center, Farmington, ConnecticutJohn Kramer - University of Connecticut Health Center, Farmington, ConnecticutSam Kuperman - University of Connecticut Health Center, Farmington, ConnecticutBernice Porjesz - University of Connecticut Health Center, Farmington, ConnecticutJay Tischfield - University of Connecticut Health Center, Farmington, ConnecticutHoward J Edenberg - University of Connecticut Health Center, Farmington, ConnecticutTatiana Foroud - University of Connecticut Health Center, Farmington, ConnecticutMarc Schuckit - University of Connecticut Health Center, Farmington, ConnecticutAlison Goate - University of Connecticut Health Center, Farmington, ConnecticutVictor Hesselbrock - University of Connecticut Health Center, Farmington, ConnecticutLaura Bierut - University of Connecticut Health Center, Farmington, Connecticut
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.153B(6), pp.1179-1188
- DOI
- 10.1002/ajmg.b.31089
- PMID
- 20468071
- PMCID
- PMC3597340
- ISSN
- 1552-4841
- eISSN
- 1552-485X
- Grant note
- U10 AA008401 || AA / National Institute on Alcohol Abuse and Alcoholism : NIAAA
- Language
- English
- Date published
- 09/2010
- Academic Unit
- Psychiatry; Stead Family Department of Pediatrics
- Record Identifier
- 9984003460002771
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