Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples.
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AuthorJohnson, Emma C
Adams, Mark J
Bucholz, Kathleen K
Chao, Michael J
Chorlian, David B
Dick, Danielle M
Edenberg, Howard J
Kendler, Kenneth S
Kuo, Sally I-Chun
McIntosh, Andrew M
Meyers, Jacquelyn L
Plawecki, Martin H
Schuckit, Marc A
Palmer, Abraham A
Edwards, Alexis C
alcohol use disorder
polygenic risk score
Journal titlePsychological medicine
Publication Begin page1147
Publication End page1156
MetadataShow full item record
AbstractBackground: Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds. Methods: We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes. Results: In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47-0.68%, p = 2.0 × 10-8-1.0 × 10-10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10-8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10-6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10-11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10-7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10-16). Conclusions: AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
CitationJohnson EC, Sanchez-Roige S, Acion L, Adams MJ, Bucholz KK, Chan G, Chao MJ, Chorlian DB, Dick DM, Edenberg HJ, Foroud T, Hayward C, Heron J, Hesselbrock V, Hickman M, Kendler KS, Kinreich S, Kramer J, Kuo SI, Kuperman S, Lai D, McIntosh AM, Meyers JL, Plawecki MH, Porjesz B, Porteous D, Schuckit MA, Su J, Zang Y, Palmer AA, Agrawal A, Clarke TK, Edwards AC. Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples. Psychol Med. 2021 May;51(7):1147-1156. doi: 10.1017/S0033291719004045. Epub 2020 Jan 20. PMID: 31955720; PMCID: PMC7405725.
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- Genome-Wide Association Study Meta-Analysis of the Alcohol Use Disorders Identification Test (AUDIT) in Two Population-Based Cohorts.
- Authors: Sanchez-Roige S, Palmer AA, Fontanillas P, Elson SL, 23andMe Research Team, the Substance Use Disorder Working Group of the Psychiatric Genomics Consortium, Adams MJ, Howard DM, Edenberg HJ, Davies G, Crist RC, Deary IJ, McIntosh AM, Clarke TK
- Issue date: 2019 Feb 1
- Alcohol and cigarette smoking consumption as genetic proxies for alcohol misuse and nicotine dependence.
- Authors: Sanchez-Roige S, Cox NJ, Johnson EO, Hancock DB, Davis LK
- Issue date: 2021 Apr 1
- The Genetic Relationship Between Alcohol Consumption and Aspects of Problem Drinking in an Ascertained Sample.
- Authors: Johnson EC, St Pierre CL, Meyers JL, Aliev F, McCutcheon VV, Lai D, Dick DM, Goate AM, Kramer J, Kuperman S, Nurnberger JI Jr, Schuckit MA, Porjesz B, Edenberg HJ, Bucholz KK, Agrawal A
- Issue date: 2019 Jun
- Polygenic Scores for Major Depressive Disorder and Risk of Alcohol Dependence.
- Authors: Andersen AM, Pietrzak RH, Kranzler HR, Ma L, Zhou H, Liu X, Kramer J, Kuperman S, Edenberg HJ, Nurnberger JI Jr, Rice JP, Tischfield JA, Goate A, Foroud TM, Meyers JL, Porjesz B, Dick DM, Hesselbrock V, Boerwinkle E, Southwick SM, Krystal JH, Weissman MM, Levinson DF, Potash JB, Gelernter J, Han S
- Issue date: 2017 Nov 1
- Evaluating risk for alcohol use disorder: Polygenic risk scores and family history.
- Authors: Lai D, Johnson EC, Colbert S, Pandey G, Chan G, Bauer L, Francis MW, Hesselbrock V, Kamarajan C, Kramer J, Kuang W, Kuo S, Kuperman S, Liu Y, McCutcheon V, Pang Z, Plawecki MH, Schuckit M, Tischfield J, Wetherill L, Zang Y, Edenberg HJ, Porjesz B, Agrawal A, Foroud T
- Issue date: 2022 Mar
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Associations of parental alcohol use disorders and parental separation with offspring initiation of alcohol, cigarette and cannabis use and sexual debut in high-risk families.McCutcheon, Vivia V; Agrawal, Arpana; Kuo, Sally I-Chun; Su, Jinni; Dick, Danielle M; Meyers, Jacquelyn L; Edenberg, Howard J; Nurnberger, John I; Kramer, John R; Kuperman, Samuel; et al. (2017-09-06)Background and aims: Parental alcohol use disorders (AUDs) and parental separation are associated with increased risk for early use of alcohol in offspring, but whether they increase risks for early use of other substances and for early sexual debut is under-studied. We focused on associations of parental AUDs and parental separation with substance initiation and sexual debut to (1) test the strength of the associations of parental AUDs and parental separation with time to initiation (age in years) of alcohol, tobacco and cannabis use and sexual debut and (2) compare the strength of association of parental AUD and parental separation with initiation. Design: Prospective adolescent and young adult cohort of a high-risk family study, the Collaborative Study on the Genetics of Alcoholism (COGA). Setting: Six sites in the United States. Participants: A total of 3257 offspring (aged 14-33 years) first assessed in 2004 and sought for interview approximately every 2 years thereafter; 1945 (59.7%) offspring had a parent with an AUD. Measurements: Diagnostic interview data on offspring substance use and sexual debut were based on first report of these experiences. Parental life-time AUD was based on their own self-report when parents were interviewed (1991-2005) for most parents, or on offspring and other family member reports for parents who were not interviewed. Parental separation was based on offspring reports of not living with both biological parents most of the time between ages 12 and 17 years. Findings: Parental AUDs were associated with increased hazards for all outcomes, with cumulative hazards ranging from 1.19 to 2.71. Parental separation was also an independent and consistent predictor of early substance use and sexual debut, with hazards ranging from 1.19 to 2.34. The strength of association of parental separation with substance initiation was equal to that of having two AUD-affected parents, and its association with sexual debut was stronger than the association of parental AUD in one or both parents. Conclusions: Parental alcohol use disorders (AUDs) and parental separation are independent and consistent predictors of increased risk for early alcohol, tobacco and cannabis use and sexual debut in offspring from families with a high risk of parental AUDs.
Characterization of Service Use for Alcohol Problems Across Generations and Sex in Adults With Alcohol Use Disorder.Bourdon, Jessica L; Tillman, Rebecca; Francis, Meredith W; Dick, Danielle M; Stephenson, Mallory; Kamarajan, Chella; Edenberg, Howard J; Kramer, John; Kuperman, Samuel; Bucholz, Kathleen K; et al. (2020-02-13)Background: There are gaps in the literature on service use (help-seeking and treatment utilization) for alcohol problems among those with alcohol use disorder (AUD). First, policy changes and cultural shifts (e.g., insurance) related to AUD have occurred over the last few decades, making it important to study generational differences. Second, multiple studies have found that females receive fewer services than males, and exploring whether these sex differences persist across generations can inform public health and research endeavors. The current study examined service use for alcohol problems among individuals with AUD. The aims were as follows: (i) to describe service use for alcohol problems; (ii) to assess generational differences (silent [b. 1928 to 1945], boomer [b. 1946 to 1964], generation X [b. 1965 to 1980], millennial [b. 1981 to 1996]) in help-seeking and treatment utilization; and (iii) to examine sex differences across generations. Methods: Data were from affected family members of probands who participated in the Collaborative Study on the Genetics of Alcoholism (N = 4,405). First, frequencies for service use variables were calculated across generations. Pearson chi-square and ANOVA were used to test for differences in rates and types of service use across generations, taking familial clustering into account. Next, Cox survival modeling was used to assess associations of generation and sex with time to first help-seeking and first treatment for AUD, and time from first onset of AUD to first help-seeking and first treatment. Interactions between generation and sex were tested within each Cox regression. Results: Significant hazards were found in all 4 transitions. Overall, younger generations used services earlier than older generations, which translated into higher likelihoods of these behaviors. Regardless of generation, younger females were less likely to use services than males. Conclusions: There are generational and sex differences in service use for alcohol problems among individuals with AUD. Policy and clinical implications are discussed.
ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry.Bierut, L J; Goate, A M; Breslau, N; Johnson, E O; Bertelsen, S; Fox, L; Agrawal, A; Bucholz, K K; Grucza, R; Hesselbrock, V; et al. (2011-10-04)A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American case-control studies in which alcohol dependence was defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and demonstrated a strong protective effect of the His48 variant (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.24, 0.48) on alcohol dependence, with genome-wide significance (6.6 × 10(-10)). The hypothesized mechanism of action involves an increased aversive reaction to alcohol; in keeping with this hypothesis, the same allele is strongly associated with a lower maximum number of drinks in a 24-hour period (lifetime), with P=3 × 10(-13). We also tested the effects of this allele on the development of alcoholism in adolescents and young adults, and demonstrated a significantly protective effect. This variant has the strongest effect on risk for alcohol dependence compared with any other tested variant in European populations.