Genome-Wide Association Study of Behavioral Disinhibition in a Selected Adolescent Sample

Jaime Derringer, Robin P. Corley, Brett C. Haberstick, Susan E. Young, Brittany A. Demmitt, Daniel P. Howrigan, Robert M. Kirkpatrick, William G. Iacono, Matt McGue, Matthew C. Keller, Sandra Brown, Susan Tapert, Christian J. Hopfer, Michael C. Stallings, Thomas J. Crowley, Soo Hyun Rhee, Ken Krauter, John K. Hewitt, Matthew B. McQueen

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Behavioral disinhibition (BD) is a quantitative measure designed to capture the heritable variation encompassing risky and impulsive behaviors. As a result, BD represents an ideal target for discovering genetic loci that predispose individuals to a wide range of antisocial behaviors and substance misuse that together represent a large cost to society as a whole. Published genome-wide association studies (GWAS) have examined specific phenotypes that fall under the umbrella of BD (e.g. alcohol dependence, conduct disorder); however no GWAS has specifically examined the overall BD construct. We conducted a GWAS of BD using a sample of 1,901 adolescents over-selected for characteristics that define high BD, such as substance and antisocial behavior problems, finding no individual locus that surpassed genome-wide significance. Although no single SNP was significantly associated with BD, restricted maximum likelihood analysis estimated that 49.3 % of the variance in BD within the Caucasian sub-sample was accounted for by the genotyped SNPs (p = 0.06). Gene-based tests identified seven genes associated with BD (p ≤ 2.0 × 10−6). Although the current study was unable to identify specific SNPs or pathways with replicable effects on BD, the substantial sample variance that could be explained by all genotyped SNPs suggests that larger studies could successfully identify common variants associated with BD.

Original languageEnglish (US)
Pages (from-to)375-381
Number of pages7
JournalBehavior genetics
Volume45
Issue number4
DOIs
StatePublished - Jul 9 2015

Keywords

  • Behavioral disinhibition
  • GWAS
  • Heritability
  • Pathway analysis

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