Alcohol Consumption Mediates the Relationship Between <i>ADH1B</i> and DSM-IV Alcohol Use Disorder and Criteria

Kilcoyne, Bari; Shmulewitz, Dvora; Meyers, Jacquelyn L.; Aharonovich, Efrat; Greenstein, Eliana; Frisch, Amos; Weizman, Abraham; Spivak, Baruch; Edenberg, Howard J.; Gelernter, Joel; Hasin, Deborah S.

doi:10.15288/jsad.2014.75.635

Cited by 10 publications

(10 citation statements)

References 36 publications

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“…49 Across these studies, the most robust association signal for rs1229984 appears to arise from Tolerance, which is notably an index of excessive consumption and consistent with the role of ADH1B in other studies of nonproblem alcohol intake. However, another study of 1130 individuals of Jewish descent reported associations between rs1229984 and both Tolerance and Desire to cut drinking.…”

Section: Discussionsupporting

confidence: 71%

“…However, another study of 1130 individuals of Jewish descent reported associations between rs1229984 and both Tolerance and Desire to cut drinking. 49 Across these studies, the most robust association signal for rs1229984 appears to arise from Tolerance, which is notably an index of excessive consumption and consistent with the role of ADH1B in other studies of nonproblem alcohol intake. 50 Plausibly, the strong findings with Desire to cut drinking might also support this as epidemiological studies have shown this criterion to index liability to less severe AD (Table S2 and Figure S7), and therefore, serve as a marker of excessive drinking, rather than severe pathology and impairment.…”

Section: Discussionsupporting

confidence: 71%

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Genome‐wide association studies of alcohol dependence, DSM‐IV criterion count and individual criteria

Lai

Wetherill

Bertelsen

et al. 2019

Genes Brain and Behavior

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Genome‐wide association studies (GWAS) of alcohol dependence (AD) have reliably identified variation within alcohol metabolizing genes (eg, ADH1B) but have inconsistently located other signals, which may be partially attributable to symptom heterogeneity underlying the disorder. We conducted GWAS of DSM‐IV AD (primary analysis), DSM‐IV AD criterion count (secondary analysis), and individual dependence criteria (tertiary analysis) among 7418 (1121 families) European American (EA) individuals from the Collaborative Study on the Genetics of Alcoholism (COGA). Trans‐ancestral meta‐analyses combined these results with data from 3175 (585 families) African‐American (AA) individuals from COGA. In the EA GWAS, three loci were genome‐wide significant: rs1229984 in ADH1B for AD criterion count (P = 4.16E−11) and Desire to cut drinking (P = 1.21E−11); rs188227250 (chromosome 8, Drinking more than intended, P = 6.72E−09); rs1912461 (chromosome 15, Time spent drinking, P = 1.77E−08). In the trans‐ancestral meta‐analysis, rs1229984 was associated with multiple phenotypes and two additional loci were genome‐wide significant: rs61826952 (chromosome 1, DSM‐IV AD, P = 8.42E−11); rs7597960 (chromosome 2, Time spent drinking, P = 1.22E−08). Associations with rs1229984 and rs18822750 were replicated in independent datasets. Polygenic risk scores derived from the EA GWAS of AD predicted AD in two EA datasets (P < .01; 0.61%‐1.82% of variance). Identified novel variants (ie, rs1912461, rs61826952) were associated with differential central evoked theta power (loss − gain; P = .0037) and reward‐related ventral striatum reactivity (P = .008), respectively. This study suggests that studying individual criteria may unveil new insights into the genetic etiology of AD liability.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionsupporting

confidence: 71%

Genome‐wide association studies of alcohol dependence, DSM‐IV criterion count and individual criteria

Lai

Wetherill

Bertelsen

et al. 2019

Genes Brain and Behavior

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“…A recently published article examined the relationship between rs1229984 and individual DSM‐IV AUD criteria in an Israeli population‐based sample (Kilcoyne et al . ). The authors found that tolerance, repeated attempts to quit, used larger amounts longer, physical/psychological problems, hazardous use and social problems were significantly associated with ADH1B .…”

Section: Discussionmentioning

confidence: 97%

Which alcohol use disorder criteria contribute to the association ofADH1Bwith alcohol dependence?

et al. 2015

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Although alcohol dependence (AD) is approximately 50% heritable, little is known about how specific genetic loci affect AD risk. In a genome-wide association study (GWAS), we identified highly significant associations between two population-specific functional variants in the alcohol dehydrogenase 1B gene (ADH1B) and AD in African-Americans (AAs; rs2066702) and European-Americans (EAs; rs1229984). In the current study, we determined which specific diagnostic criteria contributed to the observed associations of ADH1B SNPs with AD. Our analysis included both the DSM-IV and DSM-5 diagnostic systems. We also investigated the relationship of ADH1B variants to the maximum number of drinks consumed in a 24-hour period (MaxDrinks), a presumed intermediate phenotype of AD. We found that, although all criteria made strong individual contributions to the associations, the largest contributions came from those reflecting neuroadaptation: tolerance (rs2066702) and withdrawal (rs1229984). Overall, evidence for association with DSM-5 criteria was slightly stronger than for DSM-IV criteria. For rs2066702, results were similar for DSM-IV and DSM-5 criteria. However, the most significant DSM-5 criterion associated with rs1229984 was alcohol-related social/interpersonal problems. Both ADH1B variants were associated with MaxDrinks, a measure of innate tolerance, and MaxDrinks mediated the associations between ADH1B and alcohol outcomes. We replicated the findings for rs2066702 and tolerance in an independent sample of AAs. Taken together, these results suggest that variation in ADH1B affects the adaptation to heavy drinking, highlighting population-specific differences in genetic risk for AUD. They also suggest that the revisions reflected in DSM-5 AUD may enhance the utility of that diagnosis for gene finding.

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“…In addition, data used to guide the DSM-5 diagnostic thresholds and severity cut points were based largely on current disorders (Hasin et al, 2013). Although current disorders are less likely to be prone to recall biases (Grant et al, 2004), lifetime diagnoses are also relevant in contexts including identification of indications and contraindications for specific treatments, assessing risk and targeting prevention for chronologically secondary disorders , and phenotypic classifications for genetic studies (e.g., Bi et al, 2014;Kilcoyne et al, 2014). Furthermore, although the DSM-IV abuse diagnosis required only one criterion to be positive, the DSM-5 threshold of 2+ criteria has been criticized as too low on the grounds that large numbers of individuals manifesting very mild symptomatology will be diagnosed (e.g., Martin et al, 2011;Mewton et al, 2011Mewton et al, , 2013.…”

Section: Aims Of the Present Studymentioning

confidence: 99%

Nosologic Comparisons of DSM-IV and DSM-5 Alcohol and Drug Use Disorders: Results From the National Epidemiologic Survey on Alcohol and Related Conditions–III

Goldstein

Chou

Smith

et al. 2015

J. Stud. Alcohol Drugs

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ABSTRACT. Objective: The purpose of this study was to examine prevalences and concordances between Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and Fifth Edition (DSM-5) substance use disorders (SUDs) in a newly completed U.S. epidemiologic survey. Method: The National Epidemiologic Survey on Alcohol and Related Conditions-III surveyed 36,309 civilian, noninstitutionalized adults. SUDs were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-5. Concordances between DSM-IV and DSM-5 disorders were assessed using kappa statistics. Results: Prevalences of past-year substance-specific DSM-5 disorders (2+ criteria) were modestly higher than those of DSM-IV dependence and abuse combined for alcohol, sedatives/ tranquilizers, opioids, and heroin, but lower for cannabis, cocaine, and stimulants. Lifetime prevalences were lower under DSM-5. Prevalences were similar between moderate to severe (4+ criteria) DSM-5 disorders and dependence, whereas prevalences of DSM-5 disorders at 3+ criteria (DSM-5 [3+]) were higher, particularly for cannabis. Past-year concordances were excellent for DSM-IV dependence and abuse combined versus any DSM-5 and DSM-IV dependence versus DSM-5 moderate to severe disorders; lifetime concordances were fair to excellent. Past-year concordances between DSM-IV and DSM-5 (3+) were generally similar to or modestly higher than those with any DSM-5 disorder; lifetime concordances were mostly lower. Conclusions: Findings are consistent with those informing the development of DSM-5. Future research should examine differences in patterns between past-year and lifetime disorders, particularly for cannabis. Other questions warranting investigation include whether different combinations of the same numbers of criteria carry different clinical or nosologic implications, whether changes in nosology yield changes in treatment demand, and whether changes in characteristics of individuals with DSM-5 SUDs dictate modifications to screening and intervention. (J. Stud. Alcohol Drugs, 76, 378-388, 2015)

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Alcohol Consumption Mediates the Relationship Between ADH1B and DSM-IV Alcohol Use Disorder and Criteria

Cited by 10 publications

References 36 publications

Genome‐wide association studies of alcohol dependence, DSM‐IV criterion count and individual criteria

Genome‐wide association studies of alcohol dependence, DSM‐IV criterion count and individual criteria

Which alcohol use disorder criteria contribute to the association ofADH1Bwith alcohol dependence?

Nosologic Comparisons of DSM-IV and DSM-5 Alcohol and Drug Use Disorders: Results From the National Epidemiologic Survey on Alcohol and Related Conditions–III

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