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Multi-ancestry study of the genetics of problematic alcohol use in >1 million individuals.

ABSTRACT: Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. To improve our understanding of the genetics of PAU, we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals. We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine-mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and/or chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by drug repurposing analysis. Cross-ancestry polygenic risk scores (PRS) showed better performance in independent sample than single-ancestry PRS. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. The analysis of diverse ancestries contributed significantly to the findings, and fills an important gap in the literature.

SUBMITTER: Zhou H

PROVIDER: S-EPMC9901058 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Multi-ancestry study of the genetics of problematic alcohol use in >1 million individuals.

Zhou Hang H Kember Rachel L RL Deak Joseph D JD Xu Heng H Toikumo Sylvanus S Yuan Kai K Lind Penelope A PA Farajzadeh Leila L Wang Lu L Hatoum Alexander S AS Johnson Jessica J Lee Hyunjoon H Mallard Travis T TT Xu Jiayi J Johnston Keira J A KJA Johnson Emma C EC Galimberti Marco M Dao Cecilia C Levey Daniel F DF Overstreet Cassie C Byrne Enda M EM Gillespie Nathan A NA Gordon Scott S Hickie Ian B IB Whitfield John B JB Xu Ke K Zhao Hongyu H Huckins Laura M LM Davis Lea K LK Sanchez-Roige Sandra S Madden Pamela A F PAF Heath Andrew C AC Medland Sarah E SE Martin Nicholas G NG Ge Tian T Smoller Jordan W JW Hougaard David M DM Børglum Anders D AD Demontis Ditte D Krystal John H JH Gaziano J Michael JM Edenberg Howard J HJ Agrawal Arpana A Justice Amy C AC Stein Murray B MB Kranzler Henry R HR Gelernter Joel J

medRxiv : the preprint server for health sciences 20230130

Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. To improve our understanding of the genetics of PAU, we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals. We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine-mapping improved the identification of likely causal variants. Prioritizing genes th ...[more]

PMID: 36747741

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Project description:BackgroundObservational studies link moderate alcohol consumption to reduced risk of cardiometabolic diseases, including coronary heart disease (CHD) and type 2 diabetes mellitus (T2D). Mendelian randomization (MR) studies suggest that these associations are due to confounding. We present observed and genetically proxied associations between alcohol consumption and the incidence of CHD and T2D among African Americans (AA), European Americans (EA), and Hispanic Americans (HA) from the Million Veteran Program.MethodsWe conducted two retrospective, nested case-control studies of 33,053 CHD and 28,278 T2D cases matched to five controls each at the time of the event (index date). We used the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) score closest in time prior to the index date to estimate alcohol exposure. Models were adjusted for smoking, body mass index (BMI), chronic kidney disease, rheumatoid arthritis, and the use of statins or antihypertensive medications. MR analyses used either a single variant in ADH1B or a genetic score (GS) as instrumental variables.ResultsObservational analysis showed a U-shaped association of alcohol consumption with CHD and T2D risk. However, in MR analyses, neither ADH1B genotype-predicted (in 36,465 AAs, 146,464 EAs, and 11,342 HAs) nor GS-predicted (in EAs) alcohol consumption was associated with CHD risk. Similarly, T2D was not associated with alcohol consumption predicted either by ADH1B genotype (in 42,008 AAs, 109,351 EAs, and 13,538 HAs) or GS (in EAs). Multivariable MR analyses that adjusted for the effects of blood pressure and smoking also showed no association between alcohol consumption and cardiometabolic diseases.ConclusionsWe replicate prior observational studies that show a U-shaped association between alcohol consumption and cardiometabolic diseases, but MR findings show no causal association between these traits. This is largely consistent with previous MR analyses in EAs and expands the literature by providing similar findings in AA and HA populations.

Project description:PurposeThis observational study examined user characteristics, intervention use patterns, and variables associated with reductions in alcohol consumption for anonymous Internet help-seekers using a Web-based self-help program.MethodA Web-based cognitive behavioral therapy (CBT) program with eight modules delivered over 10 weeks was offered to participants with at least hazardous use of alcohol according to the Alcohol Use Disorders Identification Test (AUDIT) (n = 4165). At baseline and 10-week follow-up, participants completed the Timeline-followback (TLFB), AUDIT, Drug Use Disorders Identification Test (DUDIT), Hospital Anxiety and Depression Scale (HADS), EuroQol-5 dimension (EQ-5D), World Health Organization Quality of Life Scale-abbreviated version (WHOQOL-BREF), Readiness to Change Questionnaire (RCQ), and Readiness Ruler. Follow-up completers and non-completers were compared at baseline, and follow-up completer outcomes were reported. Predictors of change in drinking behavior were evaluated at follow-up.ResultsRegistered users were 41.88 years old on average (SD = 12.36), and 52 % were women; the mean baseline number of drinks during the past week was 27.27 (SD = 17.92) with 62 % in the AUDIT category of probable dependence and only 7 % having low-risk consumption according to public health guidelines. At follow-up (n = 1043), 53 % showed a clinically significant change to a lower level of alcohol use (χ2 = 254.403, p < 0.001); the mean alcohol consumption fell (t = 22.841, p < 0.001) and the proportion with low-risk consumption rose to 40 %. Being male, scoring higher on baseline readiness, completing the program, and accessing other support predicted low-risk drinking and clinically significant change to a lower level of alcohol use at follow-up.ConclusionA publicly available Web-based program for managing problematic alcohol use attracted users with considerable alcohol- and health-related problems, which were changed to lower severity for follow-up completers.

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Project description:BackgroundAlcohol expectancies are beliefs regarding positive (e.g., tension reduction) or negative (e.g., loss of motor coordination) effects of alcohol. Based on Social Learning Theory, social media can influence alcohol expectancies in adolescents. In particular, problematic social media use - which can reflect elements of addiction, including mood modification, tolerance, withdrawal, conflict, and relapse - could be linked to alcohol expectancies. We aimed to determine the associations between problematic social media use and alcohol expectancies in a national (U.S.) cohort of 10-14-year-old early adolescents.MethodsWe analyzed cross-sectional data from the Adolescent Brain Cognitive Development (ABCD) Study (N = 9,008) at the Year 2 assessment (2018-2020). Unadjusted and adjusted linear regression analyses were conducted to examine the associations between problematic social media use and alcohol expectancies (positive and negative), adjusting for race/ethnicity, sex, household income, parent education, sexual orientation, parental marital status, and study site. Furthermore, we computed marginal predicted probabilities to aid in interpreting findings.ResultsThe sample was 48.7% female and racially and ethnically diverse (43.0% non-White), with a mean age of 12.02 ± 0.66 years old. In models adjusted for confounders including both time spent on social media and problematic social media use, time spent on social media was not associated with positive or negative alcohol expectancies, but higher problematic social media use score was associated with higher positive (B = 0.045, 95% confidence interval [CI] 0.020-0.069) and negative (B = 0.072, 95% CI 0.043-0.101) alcohol expectancies scores.ConclusionProblematic social media use was associated with both positive and negative alcohol expectancies in a demographically diverse national sample of early adolescents in the U.S. Given the small effect sizes of the current study, future studies should further examine these relationships prospectively, as well as the mechanisms linking problematic social media use to alcohol expectancies and alcohol consumption. Because alcohol expectancies are modifiable and linked with alcohol initiation, they could be a target for future prevention efforts.

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Multi-ancestry study of the genetics of problematic alcohol use in >1 million individuals.

Publications

Multi-ancestry study of the genetics of problematic alcohol use in >1 million individuals.

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Dataset Information

Multi-ancestry study of the genetics of problematic alcohol use in >1 million individuals.

Publications

Multi-ancestry study of the genetics of problematic alcohol use in &gt;1 million individuals.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Multi-ancestry study of the genetics of problematic alcohol use in >1 million individuals.