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Plos One : Genome-wide Association Study of D-amphetamine Response in Healthy Volunteers Identifies Putative Associations, Including Cadherin 13 Cdh13, Volume 7

By Arking, Dan, E.

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Book Id: WPLBN0003938135
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : Genome-wide Association Study of D-amphetamine Response in Healthy Volunteers Identifies Putative Associations, Including Cadherin 13 Cdh13, Volume 7  
Author: Arking, Dan, E.
Volume: Volume 7
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Historic
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Publisher: Plos

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Arking, D. E. (n.d.). Plos One : Genome-wide Association Study of D-amphetamine Response in Healthy Volunteers Identifies Putative Associations, Including Cadherin 13 Cdh13, Volume 7. Retrieved from http://worldebookfair.com/


Description
Description : Both the subjective response to d-amphetamine and the risk for amphetamine addiction are known to be heritable traits. Because subjective responses to drugs may predict drug addiction, identifying alleles that influence acute response may also provide insight into the genetic risk factors for drug abuse. We performed a Genome Wide Association Study (GWAS) for the subjective responses to amphetamine in 381 non-drug abusing healthy volunteers. Responses to amphetamine were measured using a double-blind, placebo-controlled, within-subjects design. We used sparse factor analysis to reduce the dimensionality of the data to ten factors. We identified several putative associations: the strongest was between a positive subjective drug-response factor and a SNP (rs3784943) in the 8th intron of cadherin 13 (CDH13: P = 4.5861028), a gene previously associated with a number of psychiatric traits including methamphetamine dependence. Additionally, we observed a putative association between a factor representing the degree of positive affect at baseline and a SNP (rs472402) in the 1st intron of steroid-5-alpha-reductase-a-polypeptide-1 (SRD5A1: P = 2.5361027), a gene whose protein product catalyzes the rate-limiting step in synthesis of the neurosteroid allopregnanolone. This SNP belongs to an LD-block that has been previously associated with the expression of SRD5A1 and differences in SRD5A1 enzymatic activity. The purpose of this study was to begin to explore the genetic basis of subjective responses to stimulant drugs using a GWAS approach in a modestly sized sample. Our approach provides a case study for analysis of high-dimensional intermediate pharmacogenomic phenotypes, which may be more tractable than clinical diagnoses.

 

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