Evidence for genes on chromosome 2 contributing to alcohol dependence with conduct disorder and suicide attempts.
- Authors
- Dick, Danielle M; Meyers, Jacquelyn; Aliev, Fazil; Nurnberger, John; Kramer, John; Kuperman, Sam; Porjesz, Bernice; Tischfield, Jay; Edenberg, Howard J; Foroud, Tatiana; Schuckit, Marc; Goate, Alison; Hesselbrock, Victor; Bierut, Laura
- Year
- 2010
- Journal
- American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
- PMID
- 20468071
- DOI
- 10.1002/ajmg.b.31089
- PMCID
- PMC3597340
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.
Lod score graphs for each of the phenotypes using the microsatellite linkage panel across chromosome 2. Genes with empirical P<0.05 are shown according to their approximate position along the top of the graph. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
| Name | Type |
|---|---|
| ACN9 | gene |
| adult antisocial behavior | phenotype |
| AD with CD local | phenotype |
| AD with CD or SUI local | phenotype |
| African American | cohort |
| aggression | phenotype |
| alcohol | phenotype |
| alcohol dependence | phenotype |
| Alcohol Dependence Symptoms | phenotype |
| alcoholism | phenotype |
| Alcohol-related aggression | phenotype |
| alcohol withdrawal | phenotype |
| Alzheimer's disease | phenotype |
| antisocial personality disorder | phenotype |
| association sample local | cohort |
| behavioral disinhibition | phenotype |
| behavioral under-control | phenotype |
| bipolar disorder | phenotype |
| broader AD or CD or SUI phenotype local | phenotype |
| case–control sample local | cohort |
| Caucasian | cohort |
| CD | phenotype |
| Centromeric region of chromosome 2 local | drug |
| childhood conduct disorder | phenotype |
| chromosome 2 local | drug |
| Chromosome 2 local | drug |
| Chromosome 2p local | drug |
| Chromosome 2q local | drug |
| COGA adult sample local | cohort |
| COGA family sample local | cohort |
| COGA sample | cohort |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| conduct disorder | phenotype |
| controls | cohort |
| D2S379 local | variant |
| disinhibitory behavior | phenotype |
| Disinhibitory disorders | phenotype |
| drug dependence | phenotype |
| DSM-IV alcohol dependence | phenotype |
| Early-onset major depression local | phenotype |
| European ancestry | cohort |
| externalizing attempts local | phenotype |
| externalizing behavior | phenotype |
| externalizing disorders | phenotype |
| Externalizing genetic factor local | gene |
| families | cohort |
| GABRA2 | gene |
| GAW14 local | cohort |
| generalized anxiety disorder | phenotype |
| genes | gene |
| Genetic Analysis Workshop 14 local | cohort |
| genetic factors | cohort |
| habitual smoking | phenotype |
| Habitual smoking and alcohol dependence local | phenotype |
| HapMap reference samples local | cohort |
| high risk COGA family-based sample local | cohort |
| illicit drug dependence | phenotype |
| illicit drugs | phenotype |
| Illumina panel local | drug |
| impulsivity | phenotype |
| Inpatient substance abuse patients local | cohort |
| internalizing-based behavior local | phenotype |
| Internalizing genetic factor local | gene |
| Irish Affected Sib Pair Study for Alcohol Dependence local | cohort |
| major depressive disorder | phenotype |
| mesolimbic dopamine system | drug |
| microsatellite | variant |
| neurotensin | drug |
| NTSR2 local | gene |
| phenotype | phenotype |
| phobic anxiety | phenotype |
| psychostimulants | drug |
| smoking | phenotype |
| SNP | cohort |
| substance use | phenotype |
| SUI | phenotype |
| suicide | phenotype |
| Twin cohort | cohort |
| Virginia Twin Registry | cohort |
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In this knowledge base
External
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| A single-nucleus transcriptomics study of alcohol use disorder in the nucleus accumbens. | van den Oord EJCG et al. | — | 2023 | → |
| The collaborative study on the genetics of alcoholism: Sample and clinical data. | Dick DM et al. | — | 2023 | → |
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| A single-nucleus transcriptomics study of alcohol use disorder in the nucleus accumbens | van den Oord EJ et al. | — | 2022 | — |
| FOXN3 and GDNF Polymorphisms as Common Genetic Factors of Substance Use and Addictive Behaviors. | Vereczkei A et al. | — | 2022 | → |
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| Genetic variations related to inflammation in suicidal ideation and behavior: A systematic review. | Tamimou R et al. | — | 2022 | → |
| Association of PPM1G methylation with risk-taking in alcohol use disorder. | Park CI et al. | — | 2020 | → |
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