The aggregate effect of dopamine genes on dependence symptoms among cocaine users: Cross-validation of a candidate system scoring approach

Jaime Derringer, Robert F. Krueger, Danielle M. Dick, Fazil Aliev, Richard A. Grucza, Scott Saccone, Arpana Agrawal, Howard J. Edenberg, Alison M. Goate, Victor M. Hesselbrock, John R. Kramer, Peng Lin, Rosalind J. Neuman, John I. Nurnberger, John P. Rice, Jay A. Tischfield, Laura J. Bierut

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)626-635
Number of pages10
JournalBehavior genetics
Volume42
Issue number4
DOIs
StatePublished - Jul 2012
Externally publishedYes

Keywords

  • Candidate gene
  • Cocaine dependence
  • Dopamine

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Genetics(clinical)

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    Derringer, J., Krueger, R. F., Dick, D. M., Aliev, F., Grucza, R. A., Saccone, S., Agrawal, A., Edenberg, H. J., Goate, A. M., Hesselbrock, V. M., Kramer, J. R., Lin, P., Neuman, R. J., Nurnberger, J. I., Rice, J. P., Tischfield, J. A., & Bierut, L. J. (2012). The aggregate effect of dopamine genes on dependence symptoms among cocaine users: Cross-validation of a candidate system scoring approach. Behavior genetics, 42(4), 626-635. https://doi.org/10.1007/s10519-012-9531-4