The interplay between externalizing disorders polygenic risk scores and contextual factors on the development of marijuana use disorders

Jill Rabinowitz, Rashelle Jean Musci, Adam J. Milam, Kelly Benke, George R. Uhl, Danielle Y. Sisto, Nicholas S Ialongo, Brion Maher

Research output: Contribution to journalArticle

Abstract

Externalizing disorders have been extensively linked to substance use problems. However, less is known about whether genetic factors underpinning externalizing disorders and environmental features interact to predict substance use disorders (i.e., marijuana abuse and dependence) among urban African Americans. We examined whether polygenic risk scores (PRS) for conduct disorder (CD) and attention-deficit hyperactivity disorder (ADHD) interacted with contextual factors (i.e., parental monitoring, community disadvantage) to influence risk for marijuana use disorders in a sample of African American youth. Participants (N=1,050; 44.2% male) were initially recruited for an elementary school-based universal prevention trial in a Mid-Atlantic city and followed through age 20. Participants reported on their parental monitoring in sixth grade and whether they were diagnosed with marijuana abuse or dependence at age 20. Blood or saliva samples were genotyped using the Affymetrix 6.0 microarrays. The CD and ADHD PRS were created based on genome-wide association studies conducted by Dick et al. (2010) and Demontis et al. (2017), respectively. Community disadvantage was calculated based on census data when participants were in sixth grade. There was an interaction between the CD PRS and community disadvantage such that a higher CD PRS was associated with greater risk for a marijuana use disorder at higher levels of neighborhood disadvantage. This finding should be interpreted with caution owing to the number of significance tests performed. Implications for etiological models and future research directions are presented.

Original languageEnglish (US)
Pages (from-to)365-373
Number of pages9
JournalDrug and Alcohol Dependence
Volume191
DOIs
StatePublished - Oct 1 2018

Fingerprint

Cannabis
Marijuana Abuse
Conduct Disorder
Attention Deficit Disorder with Hyperactivity
African Americans
Monitoring
Genome-Wide Association Study
Censuses
Microarrays
Saliva
Substance-Related Disorders
Blood
Genes
Association reactions

Keywords

  • Attention-deficit hyperactivity disorder polygenic risk score
  • Community disadvantage
  • Conduct disorder polygenic risk score
  • Marijuana abuse and dependence
  • Parental monitoring

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

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abstract = "Externalizing disorders have been extensively linked to substance use problems. However, less is known about whether genetic factors underpinning externalizing disorders and environmental features interact to predict substance use disorders (i.e., marijuana abuse and dependence) among urban African Americans. We examined whether polygenic risk scores (PRS) for conduct disorder (CD) and attention-deficit hyperactivity disorder (ADHD) interacted with contextual factors (i.e., parental monitoring, community disadvantage) to influence risk for marijuana use disorders in a sample of African American youth. Participants (N=1,050; 44.2{\%} male) were initially recruited for an elementary school-based universal prevention trial in a Mid-Atlantic city and followed through age 20. Participants reported on their parental monitoring in sixth grade and whether they were diagnosed with marijuana abuse or dependence at age 20. Blood or saliva samples were genotyped using the Affymetrix 6.0 microarrays. The CD and ADHD PRS were created based on genome-wide association studies conducted by Dick et al. (2010) and Demontis et al. (2017), respectively. Community disadvantage was calculated based on census data when participants were in sixth grade. There was an interaction between the CD PRS and community disadvantage such that a higher CD PRS was associated with greater risk for a marijuana use disorder at higher levels of neighborhood disadvantage. This finding should be interpreted with caution owing to the number of significance tests performed. Implications for etiological models and future research directions are presented.",
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AU - Uhl, George R.

AU - Sisto, Danielle Y.

AU - Ialongo, Nicholas S

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