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

  • Salvatore, Jessica E1, 2
  • Barr, Peter B1
  • Stephenson, Mallory1
  • Aliev, Fazil1, 3
  • Kuo, Sally I-Chun1
  • Su, Jinni4
  • Agrawal, Arpana5
  • Almasy, Laura6, 7
  • Bierut, Laura5
  • Bucholz, Kathleen5
  • Chan, Grace8
  • Edenberg, Howard J9
  • Johnson, Emma C5
  • McCutcheon, Vivia V5
  • Meyers, Jacquelyn L10
  • Schuckit, Marc11
  • Tischfield, Jay12
  • Wetherill, Leah13
  • Dick, Danielle M1, 14, 15
  • 1 Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
  • 2 Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
  • 3 Department of Business Administration, Karabuk University, Karabuk, Turkey. , (Turkey)
  • 4 Department of Psychology, Arizona State University, Tempe, AZ, USA.
  • 5 Department of Psychiatry, Washington University, St Louis, MO, USA.
  • 6 Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
  • 7 Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • 8 Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA.
  • 9 Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis, IN, USA. , (India)
  • 10 Department of Psychiatry, SUNY Downstate Medical Center, Brooklyn, NY, USA.
  • 11 Department of Psychiatry, University of California-San Diego, La Jolla, CA, USA.
  • 12 Department of Genetics and the Human Genetics Institute of New Jersey, Piscataway, NJ, USA. , (Jersey)
  • 13 Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA. , (India)
  • 14 Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.
  • 15 College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, VA, USA.
Published Article
Addiction (Abingdon, England)
Publication Date
Oct 28, 2019
DOI: 10.1111/add.14815
PMID: 31659820


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). Polygenic association and sibling comparison methods. The latter strengthens inferences in observational research by controlling for confounding factors that differ between families. Six sites in the United States. 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. 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. 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%). 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). © 2019 Society for the Study of Addiction.

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