Genetic variation associated with euphorigenic effects of d-amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder.


Journal Article

Here, we extended our findings from a genome-wide association study of the euphoric response to d-amphetamine in healthy human volunteers by identifying enrichment between SNPs associated with response to d-amphetamine and SNPs associated with psychiatric disorders. We found that SNPs nominally associated (P ≤ 0.05 and P ≤ 0.01) with schizophrenia and attention deficit hyperactivity disorder were also nominally associated with d-amphetamine response. Furthermore, we found that the source of this enrichment was an excess of alleles that increased sensitivity to the euphoric effects of d-amphetamine and decreased susceptibility to schizophrenia and attention deficit hyperactivity disorder. In contrast, three negative control phenotypes (height, inflammatory bowel disease, and Parkinson disease) did not show this enrichment. Taken together, our results suggest that alleles identified using an acute challenge with a dopaminergic drug in healthy individuals can be used to identify alleles that confer risk for psychiatric disorders commonly treated with dopaminergic agonists and antagonists. More importantly, our results show the use of the enrichment approach as an alternative to stringent standards for genome-wide significance and suggest a relatively novel approach to the analysis of small cohorts in which intermediate phenotypes have been measured.

Full Text

Cited Authors

  • Hart, AB; Gamazon, ER; Engelhardt, BE; Sklar, P; Kähler, AK; Hultman, CM; Sullivan, PF; Neale, BM; Faraone, SV; Psychiatric Genomics Consortium: ADHD Subgroup, ; de Wit, H; Cox, NJ; Palmer, AA

Published Date

  • April 7, 2014

Published In

Volume / Issue

  • 111 / 16

Start / End Page

  • 5968 - 5973

PubMed ID

  • 24711425

Pubmed Central ID

  • 24711425

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.1318810111


  • eng