Hierarchical investigation of genetic influences on response inhibition in healthy young adults

Jessica Weafer, Joshua C. Gray, Kyle Hernandez, Abraham A. Palmer, James MacKillop, Harriet de Wit

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Poor inhibitory control is a known risk factor for substance use disorders, making it a priority to identify the determinants of these deficits. The aim of the current study was to identify genetic associations with inhibitory control using the stop signal task in a large sample (n = 934) of healthy young adults of European ancestry. We genotyped the subjects genome-wide and then used a hierarchical approach in which we tested seven a priori single nucleotide polymorphisms (SNPs) previously associated with stop signal task performance, approximately 9,000 SNPs designated as high-value addiction (HVA) markers by the SmokeScreen array, and approximately five million genotyped and imputed SNPs, followed by a gene-based association analysis using the resultant p values. A priori SNP analyses revealed nominally significant associations between response inhibition and one locus in HTR2A (rs6313; p = .04, dominance model, uncorrected) in the same direction as prior findings. A nominally significant association was also found in one locus in ANKK1 (rs1800497; p = .03, uncorrected), although in the opposite direction of previous reports. After accounting for multiple comparisons, the HVA, genome-wide, and gene-based analyses yielded no significant findings. This study implicates variation in serotonergic and dopaminergic genes while underscoring the difficulty of detecting the influence of individual SNPs, even when biological information is used to prioritize testing. Although such small effect sizes suggest limited utility of individual SNPs in predicting risk for addiction or other impulse control disorders, they may nonetheless shed light on complex biological processes underlying poor inhibitory control.

Original languageEnglish
Pages (from-to)512-520
Number of pages9
JournalExperimental and Clinical Psychopharmacology
Volume25
Issue number6
DOIs
StatePublished - Dec 2017

Bibliographical note

Funding Information:
This research was partially supported by National Institute on Drug Abuse Grants R01 DA032015 (Harriet de Wit), National Institute on Alcohol Abuse and Alcoholism Grant K01 AA024519 (Jessica Weafer), and the Peter Boris Chair in Addictions Research (James MacKillop). The funding sources had no other role other than financial support. All authors significantly contributed to the manuscript and have read and approved the final manuscript. None of the findings appearing in this manuscript have been presented elsewhere, including conferences, meetings, or websites. The authors thank James Baurley for providing a list of Smokescreen HVAs.

Publisher Copyright:
© 2017 American Psychological Association.

Keywords

  • Drug abuse
  • Genetics
  • Inhibitory control
  • Response inhibition
  • Stop signal task

ASJC Scopus subject areas

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

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