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

Salvatore, Jessica E.; Barr, Peter B.; Stephenson, Mallory; Alıev, Fazil; Kuo, Sally I‐Chun; Su, Jinni; Agrawal, Arpana; Almasy, Laura; Bierut, Laura J.; Bucholz, Kathleen K.; Chan, Grace; Edenberg, Howard J.; Johnson, Emma C.; Meyers, Jacquelyn L.; Schuckit, Marc A.; Tischfield, Jay A.; Wetherill, Leah; Dick, Danielle M.

doi:10.1111/add.14815

Cited by 16 publications

(16 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Later work has prioritized comparisons of between family estimates with within-family estimates to assure a lack of confounding by family background-using EA2 (34) and EA3 (23) has been a bit more mixed, with the within-family analysis often reducing the estimates of genetic penetrance by 50% compared to between-family analysis. However, even with these smaller effects, researchers have relied on this framework to show the likelihood of causal PGS effects on education and related outcomes (25,35,36). New work (36) has discussed common issues in genetic analysis that can be overcome with family-based designs, including population stratification, assortative mating, and dynastic effects.…”

Section: Discussionmentioning

confidence: 99%

The production of within-family inequality: Insights and implications of integrating genetic data

Zhao

et al. 2020

Preprint

View full text Add to dashboard Cite

The integration of genetic data within large-scale social and health surveys provides new opportunities to test long standing theories of parental investments in children and within-family inequality. Genetic predictors, called polygenic scores, allow novel assessments of young children's abilities that are uncontaminated by parental investments, and family-based samples allow indirect tests of whether children's abilities are reinforced or compensated. We use over 16,000 sibling pairs from the UK Biobank to test whether the relative ranking of siblings' polygenic scores for educational attainment is consequential for actual attainments. We find strong evidence of compensatory processes, on average, where the association between genotype and phenotype of educational attainment is reduced by over 20% for the higher-ranked sibling compared to the lower-ranked sibling. These effects are most pronounced in high socioeconomic status areas. We find no evidence that similar processes hold in the case of height or for relatives who are not full biological siblings (e.g. cousins). Our results provide a new use of polygenic scores to understand processes that generate within-family inequalities and also suggest important caveats to causal interpretations the effects of polygenic scores using siblingdifference designs.

show abstract

Section: Discussionmentioning

confidence: 99%

The production of within-family inequality: Insights and implications of integrating genetic data

Zhao

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Depression symptoms were assessed using the Center for Epidemiological Studies-Depression (CES-D) scale 99 with the caveat of the sleep disturbance question being removed due to its direct overlap with our sleep PRS measure (mean = 27.66, SD = 8.96). All regression models also included the first 10 ancestral principal components (PCs 1-10) generated in PLINK as covariates to account for population stratification as is common in Genetic and PRS analysis 100,101 .…”

Section: Covariatesmentioning

confidence: 99%

Sleep deficits and cannabis use behaviors: an analysis of shared genetics using linkage disequilibrium score regression and polygenic risk prediction

Winiger

Ellingson

Morrison

et al. 2020

Sleep

View full text Add to dashboard Cite

Study Objectives Estimate the genetic relationship of cannabis use with sleep deficits and eveningness chronotype. Methods We used linkage disequilibrium score regression (LDSC) to analyze genetic correlations between sleep deficits and cannabis use behaviors. Secondly, we generated sleep deficit polygenic risk scores (PRS) and estimated their ability to predict cannabis use behaviors using linear and logistic regression. Summary statistics came from existing genome wide association studies (GWAS) of European ancestry that were focused on sleep duration, insomnia, chronotype, lifetime cannabis use, and cannabis use disorder (CUD). A target sample for PRS prediction consisted of high-risk participants and participants from twin/family community-based studies (European ancestry; n = 760, male = 64%; mean age = 26.78 years). Target data consisted of self-reported sleep (sleep duration, feeling tired, and taking naps) and cannabis use behaviors (lifetime ever use, number of lifetime uses, past 180-day use, age of first use, and lifetime CUD symptoms). Results Significant genetic correlation between lifetime cannabis use and eveningness chronotype (rG = 0.24, p < 0.001), as well as between CUD and both short sleep duration (<7 h) (rG = 0.23, p = 0.017) and insomnia (rG = 0.20, p = 0.020). Insomnia PRS predicted earlier age of first cannabis use (OR = 0.92, p = 0.036) and increased lifetime CUD symptom count (OR = 1.09, p = 0.012). Conclusion Cannabis use is genetically associated with both sleep deficits and an eveningness chronotype, suggesting that there are genes that predispose individuals to both cannabis use and sleep deficits.

show abstract

Section: Discussionmentioning

confidence: 99%

“…We also found that genetic liability to higher educational attainment was associated with a lower risk of developing CUD, independent of ADHD or SmkInit. Observational studies have found partial evidence to support this association [10,11,56]. Using a logistic model, an effect estimate was provided in the Charitonidi et al study [11], where they found that participants with lower levels of education reported being at higher risk for weekly cannabis use (OR = 1.37, 95% CI = 1.13-1.66).…”

Section: Causal Relationship Between Cannabis Use Disorder and Educat...mentioning

confidence: 99%

Genetic support of a causal relationship between cannabis use and educational attainment: a two‐sample Mendelian randomization study of European ancestry

et al. 2022

View full text Add to dashboard Cite

Background and Aims: Excessive cannabis use may lead to lower educational attainment. However, this association may be due to confounders and reverse causality. We tested the potential causal relationship between cannabis use disorder (CUD) or life-time cannabis use (LCU) and educational attainment.Design: Bidirectional two-sample Mendelian randomization (MR) study was conducted.Our primary method was inverse-variance weighted (IVW) MR, with a series of sensitivity analyses. Multivariable MR (MVMR) was performed to estimate any direct effect independent of intelligence, smoking initiation or attention deficit hyperactivity disorder (ADHD).Setting and participants: European ancestry individuals. The sample sizes of the genome-wide association study ranged from 55 374 to 632 802 participants.Measurements: Genetic variants of CUD, LCU or educational attainment.Findings: Using univariable MR, we found evidence of a potential causal effect of genetic liability to CUD on a lower educational attainment [MR, 95% confidence interval (CI) inverse variance weighted (IVW) = −1.2 month (−1.9 month, −0.5 month); P = 0.0008]. However, we found no evidence of an effect of genetic liability to LCU on educational attainment [MR, 95% CI IVW = 0.5 month (−1.5 month, 2.6 month), P = 0.6032]. Reverse direction analysis suggested that genetic liability to higher educational attainment had a potential causal effect on lower risk of CUD [odds ratio (OR), 95% CI IVW = 0.39 (0.29, 0.52), P = 1.69 × 10 −10 ]. We also found evidence of potential causal effect from genetic liability to higher educational attainment to higher risk of LCU [OR, 95% CI IVW = 1.35(1.11, 1.66), P = 0.0033].Conclusions: Genetic liability to cannabis use disorder may lead to lower educational attainment. Genetic liability to higher educational attainment may also lead to higher life-time cannabis use risk and lower cannabis use disorder risk. However, the bidirectional effect between cannabis use disorder and educational attainment may be due to shared risk factors (e.g. attention-deficit hyperactivity disorder).

show abstract

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

Cited by 16 publications

References 47 publications

The production of within-family inequality: Insights and implications of integrating genetic data

The production of within-family inequality: Insights and implications of integrating genetic data

Sleep deficits and cannabis use behaviors: an analysis of shared genetics using linkage disequilibrium score regression and polygenic risk prediction

Genetic support of a causal relationship between cannabis use and educational attainment: a two‐sample Mendelian randomization study of European ancestry

Contact Info

Product

Resources

About