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

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

Research output: Contribution to journalArticle

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).

Original languageEnglish (US)
JournalAddiction
DOIs
StateAccepted/In press - Jan 1 2019

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Cannabis
Nicotine
Substance-Related Disorders
Tobacco Use Disorder
Alcohols
Genome-Wide Association Study
Internship and Residency
Alcoholism
Alleles
Economics
Education
Research

Keywords

  • Alcohol
  • cannabis
  • Collaborative Study on the Genetics of Alcoholism
  • nicotine
  • polygenic risk score
  • sibling comparisons

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health

Cite this

Salvatore, J. E., Barr, P. B., Stephenson, M., Aliev, F., Kuo, S. I. C., Su, J., ... Dick, D. M. (Accepted/In press). Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis. Addiction. https://doi.org/10.1111/add.14815

Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis. / Salvatore, Jessica E.; Barr, Peter B.; Stephenson, Mallory; Aliev, Fazil; Kuo, Sally I.Chun; Su, Jinni; Agrawal, Arpana; Almasy, Laura; Bierut, Laura; Bucholz, Kathleen; Chan, Grace; Edenberg, Howard J.; Johnson, Emma C.; McCutcheon, Vivia V.; Meyers, Jacquelyn L.; Schuckit, Marc; Tischfield, Jay; Wetherill, Leah; Dick, Danielle M.

In: Addiction, 01.01.2019.

Research output: Contribution to journalArticle

Salvatore, JE, Barr, PB, Stephenson, M, Aliev, F, Kuo, SIC, Su, J, Agrawal, A, Almasy, L, Bierut, L, Bucholz, K, Chan, G, Edenberg, HJ, Johnson, EC, McCutcheon, VV, Meyers, JL, Schuckit, M, Tischfield, J, Wetherill, L & Dick, DM 2019, 'Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis', Addiction. https://doi.org/10.1111/add.14815
Salvatore, Jessica E. ; Barr, Peter B. ; Stephenson, Mallory ; Aliev, Fazil ; Kuo, Sally I.Chun ; Su, Jinni ; Agrawal, Arpana ; Almasy, Laura ; Bierut, Laura ; Bucholz, Kathleen ; Chan, Grace ; Edenberg, Howard J. ; Johnson, Emma C. ; McCutcheon, Vivia V. ; Meyers, Jacquelyn L. ; Schuckit, Marc ; Tischfield, Jay ; Wetherill, Leah ; Dick, Danielle M. / Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis. In: Addiction. 2019.
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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), Fagerstr{\"o}m 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).",
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AU - Salvatore, Jessica E.

AU - Barr, Peter B.

AU - Stephenson, Mallory

AU - Aliev, Fazil

AU - Kuo, Sally I.Chun

AU - Su, Jinni

AU - Agrawal, Arpana

AU - Almasy, Laura

AU - Bierut, Laura

AU - Bucholz, Kathleen

AU - Chan, Grace

AU - Edenberg, Howard J.

AU - Johnson, Emma C.

AU - McCutcheon, Vivia V.

AU - Meyers, Jacquelyn L.

AU - Schuckit, Marc

AU - Tischfield, Jay

AU - Wetherill, Leah

AU - Dick, Danielle M.

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N2 - 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).

AB - 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).

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