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| id | Authors | First Author | Year | Title | Title/Keywords | Journal | PubMed ID | PubMed ID | DOI | Full Text (DOI) | Abstract | Keywords |
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| 1 | Acion L, Kramer J, Liu X, Chan G, Langbehn D, Bucholz K, McCutcheon V, Hesselbrock V, Schuckit M, Dick D, Hesselbrock M, Kuperman S | Acion L | 2019 | Reliability and validity of an internalizing symptom scale based on the adolescent and adult Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) | Reliability and validity of an internalizing symptom scale based on the adolescent and adult Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) | Adolescent, Adolescent Health Services, Alcohol-Related Disorders, genetics, psychology, Female, Genetic Predisposition to Disease, Humans, Interview, Psychological, Male, Personality Inventory, Prospective Studies, Reproducibility of Results, Self Report, Young Adult, Internalizing, alcoholism, scale | American Journal of Drug and Alcohol Abuse | 29870277 | 29870277 | 10.1080/00952990.2018.1476520 | 10.1080/00952990.2018.1476520 | BACKGROUND: The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) is an interview that assesses psychiatric symptoms and diagnoses, including substance use disorders and anxiety and mood (i.e., internalizing) disorders. Although the SSAGA is widely used, there exists no overall internalizing characteristics scale based on items drawn from SSAGA's mood and anxiety disorder sections. OBJECTIVES: To design and assess a SSAGA-based measurement instrument capturing the overall internalizing dimension that underlies more specific internalizing conditions. METHODS: We developed, assessed, and characterized a new scale for measuring internalizing problematic characteristics derived from the SSAGA interview. All samples were drawn from the Collaborative Studies on the Genetics of Alcoholism, a prospective multi-site genetic study of families at high risk for alcohol use disorders. All participants taking part in the study between September 2005 and September 2017 were eligible (n = 904, 52.2% female). RESULTS: The scale had adequate internal consistency (ordinal alpha = 0.85, 95% CI = [0.81, 0.89]). Construct validity was supported by its association with other measures of internalizing characteristics (Internalizing Scale from Achenbach Self Reports; Neuroticism Scale from the Neuroticism-Extraversion-Openness Five-Factor Personality Inventory). Several indices of alcohol, marijuana, and nicotine misuse were also positively associated with Internalizing Scale scores. CONCLUSIONS: The Internalizing Scale has very good psychometric properties and can be used in studies that incorporate the SSAGA interview to study the association between internalizing characteristics and problematic alcohol and other substance use. These associations can potentially be utilized to identify individuals at risk for substance problems and to design treatments targeting such individuals. | Adolescent, Adolescent Health Services, Alcohol-Related Disorders, genetics, psychology, Female, Genetic Predisposition to Disease, Humans, Interview, Psychological, Male, Personality Inventory, Prospective Studies, Reproducibility of Results, Self Report, Young Adult, Internalizing, alcoholism, scale |
| 2 | Adkins AE, Hack LM, Bigdeli TB, Williamson VS, McMichael GO, Mamdani M, Edwards AC, Aliev F, Chan RF, Bhandari P, Raabe RC, Alaimo JT, Blackwell GG, Moscati A, Poland RS, Rood B, Patterson DG, Walsh D, Collaborative Study of the Genetics of Alcoholism Consortium, Whitfield JB, Zhu G, Montgomery GW, Henders AK, Martin NG, Heath AC, Madden PAF, Frank J, Ridinger M, Wodarz N, Soyka M, Zill P, Ising M, Nothen MM, Kiefer F, Rietschel M, German Study of the Genetics of Addiction C, Gelernter J, Sherva R, Koesterer R, Almasy L, Zhao H, Kranzler HR, Farrer LA, Maher BS, Prescott CA, Dick DM, Bacanu SA, Mathies LD, Davies AG, Vladimirov VI, Grotewiel M, Bowers MS, Bettinger JC, Webb BT, Miles MF, Kendler KS, Riley BP | Adkins AE | 2017 | Genomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol-Response Behaviors in Model Organisms | Genomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol-Response Behaviors in Model Organisms | Adult, Alcoholism, diagnosis, epidemiology, genetics, Animals, Caenorhabditis elegans, Case-Control Studies, Drosophila, Ethanol, administration & dosage, Female, Genetic Loci, drug effects, genetics, Genetic Predisposition to Disease, epidemiology, genetics, Genome-Wide Association Study, methods, Humans, Ireland, epidemiology, Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Middle Aged, Models, Animal, Rats, Col6a3, Klf12, Loc339975, Ryr3, Alcohol Dependence | Alcoholism: Clinical and Experimental Research | 28226201 | 28226201 | 10.1111/acer.13362 | 10.1111/acer.13362 | BACKGROUND: Alcohol dependence (AD) shows evidence for genetic liability, but genes influencing risk remain largely unidentified. METHODS: We conducted a genomewide association study in 706 related AD cases and 1,748 unscreened population controls from Ireland. We sought replication in 15,496 samples of European descent. We used model organisms (MOs) to assess the role of orthologous genes in ethanol (EtOH)-response behaviors. We tested 1 primate-specific gene for expression differences in case/control postmortem brain tissue. RESULTS: We detected significant association in COL6A3 and suggestive association in 2 previously implicated loci, KLF12 and RYR3. None of these signals are significant in replication. A suggestive signal in the long noncoding RNA LOC339975 is significant in case:control meta-analysis, but not in a population sample. Knockdown of a COL6A3 ortholog in Caenorhabditis elegans reduced EtOH sensitivity. Col6a3 expression correlated with handling-induced convulsions in mice. Loss of function of the KLF12 ortholog in C. elegans impaired development of acute functional tolerance (AFT). Klf12 expression correlated with locomotor activation following EtOH injection in mice. Loss of function of the RYR3 ortholog reduced EtOH sensitivity in C. elegans and rapid tolerance in Drosophila. The ryanodine receptor antagonist dantrolene reduced motivation to self-administer EtOH in rats. Expression of LOC339975 does not differ between cases and controls but is reduced in carriers of the associated rs11726136 allele in nucleus accumbens (NAc). CONCLUSIONS: We detect association between AD and COL6A3, KLF12, RYR3, and LOC339975. Despite nonreplication of COL6A3, KLF12, and RYR3 signals, orthologs of these genes influence behavioral response to EtOH in MOs, suggesting potential involvement in human EtOH response and AD liability. The associated LOC339975 allele may influence gene expression in human NAc. Although the functions of long noncoding RNAs are poorly understood, there is mounting evidence implicating these genes in multiple brain functions and disorders. | Adult, Alcoholism, diagnosis, epidemiology, genetics, Animals, Caenorhabditis elegans, Case-Control Studies, Drosophila, Ethanol, administration & dosage, Female, Genetic Loci, drug effects, genetics, Genetic Predisposition to Disease, epidemiology, genetics, Genome-Wide Association Study, methods, Humans, Ireland, epidemiology, Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Middle Aged, Models, Animal, Rats, Col6a3, Klf12, Loc339975, Ryr3, Alcohol Dependence |
| 3 | Agrawal A, Bierut LJ | Agrawal A | 2012 | Identifying genetic variation for alcohol dependence | Identifying genetic variation for alcohol dependence | Alcoholism, genetics, Aldehyde Dehydrogenase, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans | Alcohol Research: Current Reviews | 23134043 | 23134043 | Researchers are using various strategies to identify the genes that may be associated with alcoholism. The initial efforts primarily relied on candidate gene and linkage studies; more recently, however, modern advances in genotyping have resulted in widespread use of genome-wide association studies for alcohol dependence. The key findings of the earlier studies were that variations (i.e., polymorphisms) in the DNA sequences of the genes encoding alcohol dehydrogenase 1B (i.e., the ADH1B gene), aldehyde dehydrogenase 2 (i.e., the ALDH2 gene), and other alcohol-metabolizing enzymes mediate the risk for alcoholism; moreover, these polymorphisms also have an impact on the risk of alcohol-related cancers, such as esophageal cancer. In addition, a gene encoding one of the receptors for the neurotransmitter gamma-aminobutyric acid (GABA) known as GABRA2 seems to have a role in the development of alcohol dependence. Genome-wide association studies now offer a host of emerging opportunities, as well as challenges, for discovering the genetic etiology of alcohol dependence and for unveiling new treatment strategies. | Alcoholism, genetics, Aldehyde Dehydrogenase, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans | ||
| 4 | Agrawal A, Brislin SJ, Bucholz KK, Dick D, Hart RP, Johnson EC, Meyers J, Salvatore J, Slesinger P, COGA Consortium, Laura Almasy, Foroud T, Goate A, Hesselbrock V, Kramer J, Kuperman S, Merikangas AK, Nurnberger JI, Tischfield J, Edenberg HJ, Porjesz B | Agrawal A | In Press | The Collaborative Study on the Genetics of Alcoholism: 1. Overview | Genes, Brain and Behavior | |||||||
| 5 | Agrawal A, Chou YL, Carey CE, Baranger DAA, Zhang B, Sherva R, Wetherill L, Kapoor M, Wang JC, Bertelsen S, Anokhin AP, Hesselbrock V, Kramer J, Lynskey MT, Meyers JL, Nurnberger JI, Rice JP, Tischfield J, Bierut LJ, Degenhardt L, Farrer LA, Gelernter J, Hariri AR, Heath AC, Kranzler HR, Madden PAF, Martin NG, Montgomery GW, Porjesz B, Wang T, Whitfield JB, Edenberg HJ, Foroud T, Goate AM, Bogdan R, Nelson EC | Agrawal A | 2018 | Genome-wide association study identifies a novel locus for cannabis dependence | Genome-wide association study identifies a novel locus for cannabis dependence | Adult, African Americans, genetics, Alleles, Cannabis, Case-Control Studies, Chromosomes, Human, Pair 10, genetics, Cohort Studies, Female, Gene Frequency, genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, methods, Genotype, Humans, Male, Marijuana Abuse, genetics, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, genetics, Whites, genetics, Young Adult | Molecular Psychiatry | 29112194 | 29112194 | 10.1038/mp.2017.200 | 10.1038/mp.2017.200 | Despite moderate heritability, only one study has identified genome-wide significant loci for cannabis-related phenotypes. We conducted meta-analyses of genome-wide association study data on 2080 cannabis-dependent cases and 6435 cannabis-exposed controls of European descent. A cluster of correlated single-nucleotide polymorphisms (SNPs) in a novel region on chromosome 10 was genome-wide significant (lowest P=1.3E-8). Among the SNPs, rs1409568 showed enrichment for H3K4me1 and H3K427ac marks, suggesting its role as an enhancer in addiction-relevant brain regions, such as the dorsolateral prefrontal cortex and the angular and cingulate gyri. This SNP is also predicted to modify binding scores for several transcription factors. We found modest evidence for replication for rs1409568 in an independent cohort of African American (896 cases and 1591 controls; P=0.03) but not European American (EA; 781 cases and 1905 controls) participants. The combined meta-analysis (3757 cases and 9931 controls) indicated trend-level significance for rs1409568 (P=2.85E-7). No genome-wide significant loci emerged for cannabis dependence criterion count (n=8050). There was also evidence that the minor allele of rs1409568 was associated with a 2.1% increase in right hippocampal volume in an independent sample of 430 EA college students (fwe-P=0.008). The identification and characterization of genome-wide significant loci for cannabis dependence is among the first steps toward understanding the biological contributions to the etiology of this psychiatric disorder, which appears to be rising in some developed nations. | Adult, African Americans, genetics, Alleles, Cannabis, Case-Control Studies, Chromosomes, Human, Pair 10, genetics, Cohort Studies, Female, Gene Frequency, genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, methods, Genotype, Humans, Male, Marijuana Abuse, genetics, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, genetics, Whites, genetics, Young Adult |
| 6 | Agrawal A, Edenberg HJ, Foroud T, Bierut LJ, Dunne G, Hinrichs AL, Nurnberger JI, Crowe R, Kuperman S, Schuckit MA, Begleiter H, Porjesz B, Dick DM | Agrawal A | 2006 | Association of GABRA2 with drug dependence in the collaborative study of the genetics of alcoholism sample | Association of GABRA2 with drug dependence in the collaborative study of the genetics of alcoholism sample | Alcoholism, genetics, Chromosome Mapping, Chromosomes, Human, Pair 4, DNA, genetics, isolation & purification, Family, Female, Humans, Male, Marijuana Abuse, genetics, Pedigree, Phenotype, Polymorphism, Single Nucleotide, Receptors, GABA-A, genetics, Substance-Related Disorders, genetics | Behavior Genetics | 16622805 | 16622805 | 10.1007/s10519-006-9069-4 | 10.1007/s10519-006-9069-4 | Results from twin studies suggest that overlapping genetic factors influence alcohol dependence and illicit drug dependence. Using data from the Collaborative Study on the Genetics of Alcoholism (COGA), we examined the association between 69 SNPs in the GABAA receptor gene cluster on chromosome 4 and marijuana and illicit drug dependence, individually, and as co-occurring phenotypes with alcohol dependence. Results suggested association between marijuana dependence and illicit drug dependence with SNPs in the GABRA2 gene. Interestingly, the evidence for association previously observed with alcohol dependence came only from individuals with comorbid illicit drug dependence. There was no association with other genes in the GABAA cluster on chromosome 4 with illicit drug dependence. | Alcoholism, genetics, Chromosome Mapping, Chromosomes, Human, Pair 4, DNA, genetics, isolation & purification, Family, Female, Humans, Male, Marijuana Abuse, genetics, Pedigree, Phenotype, Polymorphism, Single Nucleotide, Receptors, GABA-A, genetics, Substance-Related Disorders, genetics |
| 7 | Agrawal A, Edenberg HJ, Gelernter J | Agrawal A | 2016 | Meta-Analyses of Genome-Wide Association Data Hold New Promise for Addiction Genetics | Meta-Analyses of Genome-Wide Association Data Hold New Promise for Addiction Genetics | Behavior, Addictive, diagnosis, epidemiology, genetics, Case-Control Studies, Genetic Predisposition to Disease, epidemiology, genetics, Genome-Wide Association Study, statistics & numerical data, Humans, Phenotype, Statistics as Topic | Journal of Studies on Alcohol and Drugs | 27588522 | 27588522 | 10.15288/jsad.2016.77.676 | 10.15288/jsad.2016.77.676 | Meta-analyses of genome-wide association study data have begun to lead to promising new discoveries for behavioral and psychiatrically relevant phenotypes (e.g., schizophrenia, educational attainment). We outline how this methodology can similarly lead to novel discoveries in genomic studies of substance use disorders, and discuss challenges that will need to be overcome to accomplish this goal. We illustrate our approach with the work of the newly established Substance Use Disorders workgroup of the Psychiatric Genomics Consortium. | Behavior, Addictive, diagnosis, epidemiology, genetics, Case-Control Studies, Genetic Predisposition to Disease, epidemiology, genetics, Genome-Wide Association Study, statistics & numerical data, Humans, Phenotype, Statistics as Topic |
| 8 | Agrawal A, Freedman ND, Bierut LJ | Agrawal A | 2011 | Genome-wide association studies of alcohol intake--a promising cocktail? | Genome-wide association studies of alcohol intake--a promising cocktail? | Alcohol Drinking, genetics, Alcoholism, genetics, Genetic Predisposition to Disease, Genetic Variation, Genome, Genome-Wide Association Study, Humans | American Journal of Clinical Nutrition | 21367945 | 21367945 | 10.3945/ajcn.111.012641 | 10.3945/ajcn.111.012641 | Alcohol Drinking, genetics, Alcoholism, genetics, Genetic Predisposition to Disease, Genetic Variation, Genome, Genome-Wide Association Study, Humans | |
| 9 | Agrawal A, Freedman ND, Cheng YC, Lin P, Shaffer JR, Sun Q, Taylor K, Yaspan B, Cole JW, Cornelis MC, DeSensi RS, Fitzpatrick A, Heiss G, Kang JH, O'Connell J, Bennett S, Bookman E, Bucholz KK, Caporaso N, Crout R, Dick DM, Edenberg HJ, Goate A, Hesselbrock V, Kittner S, Kramer J, Nurnberger JI, Jr., Qi L, Rice JP, Schuckit M, van Dam RM, Boerwinkle E, Hu F, Levy S, Marazita M, Mitchell BD, Pasquale LR, Bierut LJ, Geneva Consortium | Agrawal A | 2012 | Measuring alcohol consumption for genomic meta-analyses of alcohol intake: opportunities and challenges | Measuring alcohol consumption for genomic meta-analyses of alcohol intake: opportunities and challenges | Alcohol Drinking, genetics, Alcoholic Beverages, Genetic Loci, Genetic Variation, Genome, Human, Genome-Wide Association Study, methods, Genotype, Humans, Meta-Analysis as Topic, Quantitative Trait, Heritable | American Journal of Clinical Nutrition | 22301922 | 22301922 | 10.3945/ajcn.111.015545 | 10.3945/ajcn.111.015545 | Whereas moderate drinking may have health benefits, excessive alcohol consumption causes many important acute and chronic diseases and is the third leading contributor to preventable death in the United States. Twin studies suggest that alcohol-consumption patterns are heritable (50%); however, multiple genetic variants of modest effect size are likely to contribute to this heritable variation. Genome-wide association studies provide a tool for discovering genetic loci that contribute to variations in alcohol consumption. Opportunities exist to identify susceptibility loci with modest effect by meta-analyzing together multiple studies. However, existing studies assessed many different aspects of alcohol use, such as typical compared with heavy drinking, and these different assessments can be difficult to reconcile. In addition, many studies lack the ability to distinguish between lifetime and recent abstention or to assess the pattern of drinking during the week, and a variety of such concerns surround the appropriateness of developing a common summary measure of alcohol intake. Combining such measures of alcohol intake can cause heterogeneity and exposure misclassification, cause a reduction in power, and affect the magnitude of genetic association signals. In this review, we discuss the challenges associated with harmonizing alcohol-consumption data from studies with widely different assessment instruments, with a particular focus on large-scale genetic studies. | Alcohol Drinking, genetics, Alcoholic Beverages, Genetic Loci, Genetic Variation, Genome, Human, Genome-Wide Association Study, methods, Genotype, Humans, Meta-Analysis as Topic, Quantitative Trait, Heritable |
| 10 | Agrawal A, Hinrichs AL, Dunn G, Bertelsen S, Dick DM, Saccone SF, Saccone NL, Grucza RA, Wang JC, Cloninger CR, Edenberg HJ, Foroud T, Hesselbrock V, Kramer J, Bucholz KK, Kuperman S, Nurnberger JI, Jr., Porjesz B, Schuckit MA, Goate AM, Bierut LJ | Agrawal A | 2008 | Linkage scan for quantitative traits identifies new regions of interest for substance dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample | Linkage scan for quantitative traits identifies new regions of interest for substance dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample | Adolescent, Adult, Aged, Aged, 80 and over, Alcoholism, diagnosis, genetics, Chromosomes, Human, Pair 1, genetics, Chromosomes, Human, Pair 10, genetics, Chromosomes, Human, Pair 13, genetics, Chromosomes, Human, Pair 14, genetics, Chromosomes, Human, Pair 2, genetics, Diagnostic and Statistical Manual of Mental Disorders, Genetic Linkage, genetics, Genotype, Humans, Illicit Drugs, Marijuana Abuse, diagnosis, genetics, Middle Aged, Pedigree, Polymorphism, Single Nucleotide, genetics, Substance-Related Disorders, diagnosis, genetics, Twins, genetics | Drug and Alcohol Dependence | 17942244 | 17942244 | 10.1016/j.drugalcdep.2007.08.015 | 10.1016/j.drugalcdep.2007.08.015 | Dependence on alcohol and illicit drugs frequently co-occur. Results from a number of twin studies suggest that heritable influences on alcohol dependence and drug dependence may substantially overlap. Using large, genetically informative pedigrees from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed quantitative linkage analyses using a panel of 1717 SNPs. Genome-wide linkage analyses were conducted for quantitative measures of DSM-IV alcohol dependence criteria, cannabis dependence criteria and dependence criteria across any illicit drug (including cannabis) individually and in combination as an average score across alcohol and illicit drug dependence criteria. For alcohol dependence, LOD scores exceeding 2.0 were noted on chromosome 1 (2.0 at 213 cM), 2 (3.4 at 234 cM) and 10 (3.7 at 60 cM). For cannabis dependence, a maximum LOD of 1.9 was noted at 95 cM on chromosome 14. For any illicit drug dependence, LODs of 2.0 and 2.4 were observed on chromosome 10 (116 cM) and 13 (64 cM) respectively. Finally, the combined alcohol and/or drug dependence symptoms yielded LODs >2.0 on chromosome 2 (3.2, 234 cM), 10 (2.4 and 2.6 at 60 cM and 116 cM) and 13 (2.1 at 64 cM). These regions may harbor genes that contribute to the biological basis of alcohol and drug dependence. | Adolescent, Adult, Aged, Aged, 80 and over, Alcoholism, diagnosis, genetics, Chromosomes, Human, Pair 1, genetics, Chromosomes, Human, Pair 10, genetics, Chromosomes, Human, Pair 13, genetics, Chromosomes, Human, Pair 14, genetics, Chromosomes, Human, Pair 2, genetics, Diagnostic and Statistical Manual of Mental Disorders, Genetic Linkage, genetics, Genotype, Humans, Illicit Drugs, Marijuana Abuse, diagnosis, genetics, Middle Aged, Pedigree, Polymorphism, Single Nucleotide, genetics, Substance-Related Disorders, diagnosis, genetics, Twins, genetics |
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