Linkage scan of alcohol dependence in the UCSF Family Alcoholism Study.
- Authors
- Gizer, Ian R; Ehlers, Cindy L; Vieten, Cassandra; Seaton-Smith, Kimberly L; Feiler, Heidi S; Lee, James V; Segall, Samantha K; Gilder, David A; Wilhelmsen, Kirk C
- Year
- 2011
- Journal
- Drug and alcohol dependence
- PMID
- 20817416
- DOI
- 10.1016/j.drugalcdep.2010.07.017
- PMCID
- PMC3008755
Ample data suggest that alcohol dependence represents a heritable condition, and several research groups have performed linkage analysis to identify genomic regions influencing this disorder. In the present study, a genome-wide linkage scan for alcohol dependence was conducted in a community sample of 565 probands and 1080 first-degree relatives recruited through the UCSF Family Alcoholism Study. The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was used to derive DSM-IV alcohol dependence diagnoses. Although no loci achieved genome-wide significance (i.e., LOD score > 3.0), several linkage peaks of interest (i.e., LOD score > 1.0) were identified. When the strict DSM-IV alcohol dependence diagnosis requiring the temporal clustering of symptoms served as the phenotype, linkage peaks were identified on chromosomes 1p36.31-p36.22, 2q37.3, 8q24.3, and 18p11.21-p11.2. When the temporal clustering of symptoms was not required, linkage peaks were again identified on chromosomes 1p36.31-p36.22 and 8q24.3 as well as novel loci on chromosomes 1p22.3, 2p24.3-p24.1, 9p24.1-p23, and 22q12.3-q13.1. Follow-up analyses were conducted by performing linkage analysis for the 12 alcohol dependence symptoms assessed by the SSAGA across the support intervals for the observed linkage peaks. These analyses demonstrated that different collections of symptoms often assessing distinct aspects of alcohol dependence (e.g., uncontrollable drinking and withdrawal vs. tolerance and drinking despite health problems) contributed to each linkage peak and often yielded LOD scores exceeding that reported for the alcohol dependence diagnosis. Such findings provide insight into how specific genomic regions may influence distinct aspects of alcohol dependence.
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| Name | Type |
|---|---|
| 1647 individuals local | cohort |
| 177 families local | cohort |
| 18p11.21–p11.2 local | anatomy |
| 1p22.3 local | variant |
| 1p36.31–p36.22 local | anatomy |
| 22q12.3-13.1 local | variant |
| 713 families local | cohort |
| 875 individuals local | cohort |
| 8q24.3 local | anatomy |
| 9p24.1-p23 local | variant |
| ADH gene cluster | gene |
| Age-of-onset local | phenotype |
| alcohol | phenotype |
| alcohol dependence | phenotype |
| Alcohol dependence diagnosis without temporal clustering required local | phenotype |
| Alcohol dependence diagnosis with temporal clustering required local | phenotype |
| Alcohol Dependence Symptoms | phenotype |
| alcohol misuse phenotypes local | phenotype |
| Alcohol related life events local | phenotype |
| alcohol-related phenotypes | phenotype |
| alcohol sensitivity | phenotype |
| Alcohol Use Disorder | phenotype |
| antisocial personality disorder | phenotype |
| anxiety | phenotype |
| binge drinking | phenotype |
| bipolar disorder | phenotype |
| Broader definition local | phenotype |
| Chromosomal region local | variant |
| Chromosome 19 local | variant |
| Chromosome 1 locus at 11 cM local | variant |
| Chromosome 1p local | variant |
| Chromosome 1 region 114 cM local | anatomy |
| Chromosome 1 region 12 cM local | anatomy |
| chromosome 22 local | variant |
| Chromosome 2 region 32 cM local | anatomy |
| chromosome 4q local | variant |
| Chromosome 8 locus local | variant |
| Chromosome 8 region local | anatomy |
| chromosome 9 local | variant |
| Chromosome 9 local | variant |
| Chromosome 9 region 18 cM local | anatomy |
| cocaine | phenotype |
| Collaborative Studies on the Genetics of Alcoholism | cohort |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| conduct disorder | phenotype |
| Continued drinking despite physical health problem local | phenotype |
| Continued drinking despite psychological problems local | phenotype |
| control participants | cohort |
| Dependence symptoms | phenotype |
| depression | phenotype |
| drinking | phenotype |
| drug dependence | phenotype |
| DSM-III-R alcohol dependence | phenotype |
| DSM-IV alcohol dependence | phenotype |
| DSM-IV symptom cluster local | phenotype |
| DSM-IV symptom clusters local | phenotype |
| family-based sample | cohort |
| Full DSM-IV criteria local | phenotype |
| GABAA receptor subunit gene cluster | gene |
| general population sample | cohort |
| Inability to quit drinking local | phenotype |
| Inability to reduce drinking local | phenotype |
| Intravenous substance use local | drug |
| Life-threatening illness local | phenotype |
| medical/mental health problems local | phenotype |
| medical/mental health symptoms local | phenotype |
| Medical/mental health symptoms local | phenotype |
| Medical or mental health problems local | phenotype |
| Native Americans | cohort |
| opiates | drug |
| Persistent drinking local | phenotype |
| Personality characteristics related to addiction local | phenotype |
| Prescott et al. 2006 local | cohort |
| Reduced social and occupational functioning due to drinking local | phenotype |
| Reward dependence local | phenotype |
| schizophrenia | phenotype |
| severe drinking local | phenotype |
| Severe drinking local | phenotype |
| severe drinking symptoms local | phenotype |
| Severe drinking symptoms local | phenotype |
| Short-term consequences of drinking local | phenotype |
| Spending significant time drinking local | phenotype |
| stimulants | drug |
| substance use | phenotype |
| Temporal clustering of symptoms local | phenotype |
| tolerance | phenotype |
| UCSF Family Alcoholism Study | cohort |
| UCSF Family Study local | cohort |
| UCSF sample local | cohort |
| withdrawal | phenotype |
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| The genetics of substance dependence. | 2012 | 22703173 |
| Linkage analyses of cannabis dependence, craving, and withdrawal in the San Francisco family study. | 2010 | 19937978 |
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| Convergent Pathways Identified for Cannabis Use Disorder Across Diverse Ancestry Populations | Peng Q et al. | — | 2025 | — |
| Genetic risk for alcohol use disorder in relation to individual symptom criteria: Do polygenic indices provide unique information for understanding severity and heterogeneity? | Sarles YM et al. | — | 2025 | → |
| Pleiotropic loci for cannabis use disorder severity in multi-ancestry high-risk populations. | Peng Q et al. | — | 2023 | → |
| Association of Predicted Expression and Multimodel Association Analysis of Substance Abuse Traits. | Bost DM et al. | — | 2022 | → |
| Genetic loci for alcohol-related life events and substance-induced affective symptoms: indexing the "dark side" of addiction. | Peng Q et al. | — | 2019 | → |
| Statistical Methods and Software for Substance Use and Dependence Genetic Research. | Lan T et al. | — | 2019 | → |
| An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice. | Metten P et al. | — | 2018 | → |
| Associations Between Genomic Variants in Alcohol Dehydrogenase Genes and Alcohol Symptomatology in American Indians and European Americans: Distinctions and Convergence. | Peng Q et al. | — | 2017 | → |
| The genetics of alcohol dependence and alcohol-related liver disease. | Stickel F et al. | — | 2017 | → |
| Genetics of alcoholism. | Iyer-Eimerbrink PA et al. | — | 2014 | → |
| Mpdz expression in the caudolateral substantia nigra pars reticulata is crucially involved in alcohol withdrawal. | Kruse LC et al. | — | 2014 | → |
| The genetics of alcohol dependence. | Rietschel M et al. | — | 2013 | → |
| Genome-wide linkage scan of antisocial behavior, depression, and impulsive substance use in the UCSF family alcoholism study. | Gizer IR et al. | — | 2012 | → |
| The genetics of substance dependence. | Wang JC et al. | — | 2012 | → |
| Linkage analyses of cannabis dependence, craving, and withdrawal in the San Francisco family study. | Ehlers CL et al. | — | 2010 | → |