Polygenic risk, personality dimensions, and adolescent alcohol use problems: A longitudinal study

James J. Li*, Jeanne E. Savage, Kenneth S. Kendler, Matthew Hickman, Liam Mahedy, John Macleod, Jaakko Kaprio, Richard J. Rose, Danielle M. Dick

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Objective: Alcohol use problems are common during adolescence and can predict serious negative outcomes in adulthood, including substance dependence and psychopathology. The current study examines the notion that alcohol use problems are driven by polygenic influences and that genetic influences may indirectly affect alcohol use problems through multiple pathways of risk, including variations in personality. Method: We used a genome-wide approach to examine associations between genetic risk for alcohol use problems, personality dimensions, and adolescent alcohol use problems in two separate longitudinal population-based samples, the Finnish Twin Cohort (FinnTwin12) and the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were 1,035 young adults from FinnTwin12 and 3,160 adolescents from ALSPAC. Polygenic risk scores (PRS) were calculated for ALSPAC using genome-wide association results (on alcohol dependence symptoms as defined by the Diagnostic and Statistical Manual of Men- tal Disorders, Fourth Edition) from FinnTwin12. A parallel multiple mediator model was tested to examine whether the association between PRS and alcohol use problems assessed at age 16 could be explained by variations in personality dimensions assessed at age 13, including sensation seeking and negative emotionality. Results: PRS were marginally predictive of age 16 alcohol use problems; this association was partially mediated by sensation seeking. Polygenic variation underlying risk for alcohol use problems may directly influence the effects of sensation seeking, which in turn influence the development of alcohol use problems in later adolescence. Conclusions: These findings contribute to the increasing evidence regarding the salience of sensation seeking during early adolescence as a potential constituent in the risk pathway underlying the development of alcohol use problems.

Original languageEnglish
Pages (from-to)442-451
Number of pages10
JournalJournal of Studies on Alcohol and Drugs
Volume78
Issue number3
DOIs
Publication statusPublished - 1 Jan 2017
Externally publishedYes

Funding

The UK Medical Research Council and the Wellcome Trust (Grant ref: 092731) and the University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children. This publication is the work of the authors and the corresponding author will serve as guarantor for the contents of this article. Various authors on this project were supported by the National Institute on Alcohol Abuse and Alcoholism (Grants R01-AA014516 and R01-AA018333 to Danielle M. Dick, and Grant K02-AA018755 to Jeanne E. Savage), and a core grant to the Waisman Center from the National Institute on Child Health and Human Development (P30-HD03352). The MRC and Alcohol Research UK (MR/L022206/1) supports Liam Mahedy. Genome-wide association study data were generated by Sample Logistics and Genotyping Facilities at the Wellcome Trust Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23 and Me. Data collection and genotyping in FinnTwin12 was supported by National Institute on Alcohol Abuse and Alcoholism Grants R01-AA-12502, R01-AA-00145, R01-AA-09203; the Academy of Finland Center of Excellence in Complex Disease Genetics Grants 213506, 129680; and the Academy of Finland Grants 265240, 263278, 264146, 118555, and 141054. The authors are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses.

FundersFunder number
Academy of Finland Center of Excellence in Complex Disease Genetics213506, 129680
MRC and Alcohol Research UKMR/L022206/1
Wellcome Trust Sanger InstituteR01-AA-09203, R01-AA-12502, R01-AA-00145
National Institute on Alcohol Abuse and AlcoholismR01-AA014516, K02-AA018755, R01-AA018333, R01AA012502
National Institute of Child Health and Human DevelopmentP30-HD03352
Center for Outcomes Research and Evaluation, Yale School of Medicine
Waisman Center
Wellcome Trust092731
Research Councils UK
University of Bristol
Academy of Finland141054, 264146, 118555, 263278, 265240

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