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The Aggregate Effect of Dopamine Genes on Dependence Symptoms Among Cocaine Users: Cross-Validation of a Candidate System Scoring Approach.

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Title: The Aggregate Effect of Dopamine Genes on Dependence Symptoms Among Cocaine Users: Cross-Validation of a Candidate System Scoring Approach.
Authors: Derringer, Jaime, Krueger, Robert, Dick, Danielle, Aliev, Fazil, Grucza, Richard, Saccone, Scott, Agrawal, Arpana, Edenberg, Howard, Goate, Alison, Hesselbrock, Victor, Kramer, John, Lin, Peng, Neuman, Rosalind, Nurnberger, John, Rice, John, Tischfield, Jay, Bierut, Laura
Source: Behavior Genetics. Jul2012, Vol. 42 Issue 4, p626-635. 10p. 2 Charts, 1 Graph.
Subjects: Dopamine, Cocaine, Lymphoblastoid cell lines, Interviewing, Psychometrics, Quantitative research, Physiology
Abstract: Genome-wide studies of psychiatric conditions frequently fail to explain a substantial proportion of variance, and replication of individual SNP effects is rare. We demonstrate a selective scoring approach, in which variants from several genes known to directly affect the dopamine system are considered concurrently to explain individual differences in cocaine dependence symptoms. 273 SNPs from eight dopamine-related genes were tested for association with cocaine dependence symptoms in an initial training sample. We identified a four-SNP score that accounted for 0.55% of the variance in a separate testing sample ( p = 0.037). These findings suggest that (1) limiting investigated SNPs to those located in genes of theoretical importance improves the chances of identifying replicable effects by reducing statistical penalties for multiple testing, and (2) considering top-associated SNPs in the aggregate can reveal replicable effects that are too small to be identified at the level of individual SNPs. [ABSTRACT FROM AUTHOR]
Copyright of Behavior Genetics is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Genome-wide studies of psychiatric conditions frequently fail to explain a substantial proportion of variance, and replication of individual SNP effects is rare. We demonstrate a selective scoring approach, in which variants from several genes known to directly affect the dopamine system are considered concurrently to explain individual differences in cocaine dependence symptoms. 273 SNPs from eight dopamine-related genes were tested for association with cocaine dependence symptoms in an initial training sample. We identified a four-SNP score that accounted for 0.55% of the variance in a separate testing sample ( p = 0.037). These findings suggest that (1) limiting investigated SNPs to those located in genes of theoretical importance improves the chances of identifying replicable effects by reducing statistical penalties for multiple testing, and (2) considering top-associated SNPs in the aggregate can reveal replicable effects that are too small to be identified at the level of individual SNPs. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Behavior Genetics is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – SubjectFull: Lymphoblastoid cell lines
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