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

Year: 2010
Type: article
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.
DOI: 10.1002/ajmg.b.31089
Authors: 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
Institutions: Virginia Commonwealth University, Indiana University School of Medicine, University of Iowa, SUNY Downstate Health Sciences University, Rutgers, The State University of New Jersey, University of California San Diego, Washington University in St. Louis, UConn Health
Language: English
Subfield: Genetics
Open Access status: bronze
Funders: State University of New York, Washington University in St. Louis, University of Connecticut, Johns Hopkins University, Virginia Commonwealth University, National Alliance for Research on Schizophrenia and Depression, National Institutes of Health, SUNY Downstate Medical Center, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, National Human Genome Research Institute
Awards: G1083756078, G1187501382, G2481876672, GENOTYPING FOR LOCATING HUMAN DISEASE GENES, G5184311545, G5359555627, G5780424650, G7047943440, G853394594, G9000025954, G9000036580
OpenAlex ID: W2127783286
FWCI: 2.178
Cites: 70
Cited by: 39
Related to: 10