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

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

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Faraone, Stephen V. De Wit, Harriet Palmer, Abraham A. Engelhardt, Barbara E. Gamazon, Eric R. Neale, Benjamin M. Cox, Nancy J. Sklar, Pamela Hart, Amy B. Kähler, Anna K. Hultman, Christina M. Sullivan, Patrick F.
Description	Author Affiliation: Hart AB ( Departments of Human Genetics, Medicine, and Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL 60637.);
Abstract	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.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	16
Volume Number	111
Language	English
Publisher	National Academy of Sciences
Publisher Date	2014-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Attention Deficit Disorder With Hyperactivity Drug Therapy Genetics Dextroamphetamine Therapeutic Use Euphoria Genetic Variation Schizophrenia Bipolar Disorder Pharmacology Drug Effects Genetic Predisposition To Disease Phenotype Polymorphism, Single Nucleotide Protective Agents Reproducibility Of Results Risk Factors Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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