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
- 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
- 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
- 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.
The role of adolescent social relationships in promoting alcohol resistance: Interrupting the intergenerational transmission of alcohol misuseStephenson, Mallory; Aliev, Fazil; Kuo, Sally I-Chun; Edwards, Alexis C.; Pandey, Gayathri; Su, Jinni; Kamarajan, Chella; Dick, Danielle; Salvatore, Jessica E. (Cambridge University Press (CUP), 2022-08-12)Genetic factors contribute to the intergenerational transmission of alcohol misuse, but not all individuals at high genetic risk develop problems. The present study examined adolescent relationships with parents, peers, and romantic partners as predictors of realized resistance, defined as high biological risk for disorder combined with a healthy outcome, to alcohol initiation, heavy episodic drinking, and alcohol use disorder (AUD). Data were from the Collaborative Study on the Genetics of Alcoholism (N = 1,858; 49.9% female; mean age at baseline = 13.91 years). Genetic risk, indexed using family history density and polygenic risk scores for alcohol problems and AUD, was used to define alcohol resistance. Adolescent predictors included parent-child relationship quality, parental monitoring, peer drinking, romantic partner drinking, and social competence. There was little support for the hypothesis that social relationship factors would promote alcohol resistance, with the exception that higher father-child relationship quality was associated with higher resistance to alcohol initiation (βˆ= −0.19, 95% CI = −0.35, −0.03). Unexpectedly, social competence was associated with lower resistance to heavy episodic drinking (βˆ= 0.10, 95% CI = 0.01, 0.20). This pattern of largely null effects underscores how little is known about resistance processes among those at high genetic risk for AUD.
Pathways to post-traumatic stress disorder and alcohol dependence: Trauma, executive functioning, and family history of alcoholism in adolescents and young adults.Subbie-Saenz de Viteri, Stacey; Pandey, Ashwini; Pandey, Gayathri; Kamarajan, Chella; Smith, Rebecca; Anokhin, Andrey; Bauer, Lance; Bender, Annah; Chan, Grace; Dick, Danielle; et al. (2020-09-29)Introduction: Family history (FH) of alcohol dependence is likely to increase the risk of trauma exposure, post-traumatic stress disorder (PTSD), and alcohol dependence. FH of alcohol dependence and trauma has been separately shown to adversely affect planning/problem-solving aspects of executive function. However, few studies have examined these risk factors in an integrated model. Methods: Using data from trauma-exposed individuals from the Collaborative Study on the Genetics of Alcoholism prospective cohort (N = 1,860), comprising offspring from alcohol-dependent high-risk and comparison families (mean age [SE] = 21.9 [4.2]), we investigated associations of trauma (nonsexual assaultive, nonassaultive, sexual assaultive) with DSM-IV PTSD and alcohol dependence symptom counts, and planning/problem-solving abilities assessed using the Tower of London Test (TOLT). Moderating effects of family history density of alcohol use disorder (FHD) on these associations and sex differences were explored. Results: Family history density was positively associated with PTSD in female participants who endorsed a sexual assaultive trauma. Exposure to nonsexual assaultive trauma was associated with more excess moves made on the TOLT. Conclusion: Findings from this study demonstrate associations with PTSD and alcohol dependence symptom counts, as well as poor problem-solving ability in trauma-exposed individuals from families densely affected with alcohol dependence, depending on trauma type, FHD, and sex. This suggests that having a FH of alcohol dependence and exposure to trauma during adolescence may be associated with more PTSD and alcohol dependence symptoms, and poor problem-solving abilities in adulthood.