Dataset Information

Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis.

ABSTRACT:

Background and aims

The associations between low educational attainment and substance use disorders (SUDs) may be related to a common genetic vulnerability. We aimed to elucidate the associations between polygenic scores for educational attainment and clinical criterion counts for three SUDs (alcohol, nicotine and cannabis).

Design

Polygenic association and sibling comparison methods. The latter strengthens inferences in observational research by controlling for confounding factors that differ between families.

Setting

Six sites in the United States.

Participants

European ancestry participants aged 25 years and older from the Collaborative Study on the Genetics of Alcoholism (COGA). Polygenic association analyses included 5582 (54% female) participants. Sibling comparisons included 3098 (52% female) participants from 1226 sibling groups nested within the overall sample.

Measurements

Outcomes included criterion counts for DSM-5 alcohol use disorder (AUDSX), Fagerström nicotine dependence (NDSX) and DSM-5 cannabis use disorder (CUDSX). We derived polygenic scores for educational attainment (EduYears-GPS) using summary statistics from a large (> 1 million) genome-wide association study of educational attainment.

Findings

In polygenic association analyses, higher EduYears-GPS predicted lower AUDSX, NDSX and CUDSX [P < 0.01, effect sizes (R² ) ranging from 0.30 to 1.84%]. These effects were robust in sibling comparisons, where sibling differences in EduYears-GPS predicted all three SUDs (P < 0.05, R² 0.13-0.20%).

Conclusions

Individuals who carry more alleles associated with educational attainment tend to meet fewer clinical criteria for alcohol, nicotine and cannabis use disorders, and these effects are robust to rigorous controls for potentially confounding factors that differ between families (e.g. socio-economic status, urban-rural residency and parental education).

SUBMITTER: Salvatore JE

PROVIDER: S-EPMC7034661 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis.

Salvatore Jessica E JE Barr Peter B PB Stephenson Mallory M Aliev Fazil F Kuo Sally I-Chun SI Su Jinni J Agrawal Arpana A Almasy Laura L Bierut Laura L Bucholz Kathleen K Chan Grace G Edenberg Howard J HJ Johnson Emma C EC McCutcheon Vivia V VV Meyers Jacquelyn L JL Schuckit Marc M Tischfield Jay J Wetherill Leah L Dick Danielle M DM

Addiction (Abingdon, England) 20191028 2

<h4>Background and aims</h4>The associations between low educational attainment and substance use disorders (SUDs) may be related to a common genetic vulnerability. We aimed to elucidate the associations between polygenic scores for educational attainment and clinical criterion counts for three SUDs (alcohol, nicotine and cannabis).<h4>Design</h4>Polygenic association and sibling comparison methods. The latter strengthens inferences in observational research by controlling for confounding factor ...[more]

PMID: 31659820

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Project description:Background and aimsMolecular genetic studies of alcohol and nicotine use have identified many genome-wide association study (GWAS) loci. We measured associations between drinking and smoking polygenic scores (PGS) and trajectories of alcohol and nicotine use outcomes from late childhood to early adulthood, substance-specific versus broader-liability PGS effects, and if PGS performance varied for consumption versus problematic substance use.Design, setting, participants and measurementsWe fitted latent growth curve models with structured residuals to scores on measures of alcohol and nicotine use and problems from ages 14 to 34 years. We then estimated associations between the intercept (initial status) and slope (rate of change) parameters and PGSs for drinks per week (DPW), problematic alcohol use (PAU), cigarettes per day (CPD) and ever being a regular smoker (SMK), controlling for sex and genetic principal components. All data were analyzed in the United States. PGSs were calculated for participants of the Minnesota Twin Family Study (n = 3225) using results from the largest GWAS of alcohol and nicotine consumption and problematic use to date.FindingsEach PGS was associated with trajectories of use for their respective substances [i.e. DPW (βmean = 0.08; βrange = 0.02-0.12) and PAU (βmean = 0.12; βrange = -0.02 to 0.31) for alcohol; CPD (βmean = 0.08; βrange = 0.04-0.14) and SMK (βmean = 0.18; βrange = 0.05-0.36) for nicotine]. The PAU and SMK PGSs also exhibited cross-substance associations (i.e. PAU for nicotine-specific intercepts and SMK for alcohol intercepts and slope). All identified SMK PGS effects remained as significant predictors of nicotine and alcohol trajectories (βmean = 0.15; βrange = 0.02-0.33), even after adjusting for the respective effects of all other PGSs.ConclusionsSubstance use-related polygenic scores (PGSs) vary in the strength and generality versus specificity of their associations with substance use and problems over time. The regular smoking PGS appears to be a robust predictor of substance use trajectories and seems to measure both nicotine-specific and non-specific genetic liability for substance use, and potentially externalizing problems in general.

Dataset Information

Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis.

Background and aims

Design

Setting

Participants

Measurements

Findings

Conclusions

Publications

Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis.

Similar Datasets

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