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Pathway based analysis of genotypes in relation to alcohol dependence

The Pharmacogenomics Journal volume 12, pages 342–348 (2012)Cite this article

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Abstract

We introduce a method for detecting variants in several genes of related function with small effect on a phenotype of interest. Our method uses logistic regression to test whether multiple alleles within a functional set have significantly higher than expected predictive value, even though none individually may have strong individual effects. We illustrate this method by testing seven gene sets (including 48 genes), from a study with1350 single nucleotide polymorphisms in 130 addiction candidate genes studied in a sample of 575 alcohol dependence (AD) cases and 530 controls. We conclude that AD is related to variation in genes participating in Glutamate and γ-amino butyric acid signaling, as has been reported elsewhere, and in stress response pathways, but not with genes in several other systems implicated in other drugs of abuse.

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Acknowledgements

We are grateful to the study participants and their families for their time and effort. FA O’Neill, the Northern Ireland Blood Transfusion Service of the British National Health Service and the Irish Garda provided assistance in obtaining control blood samples. Funding: this work was funded by U.S. National Institutes of Health Grant R01-AA-11408 and P20 AA017828, with support from the Irish Health Research Board.

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Authors and Affiliations

  1. Department of Biostatistics, Virginia Commonwealth University, Richmond, VA, USA

    M A Reimers

  2. Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA

    B P Riley, G Kalsi & K S Kendler

  3. Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA

    B P Riley & K S Kendler

  4. Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA

    B P Riley, G Kalsi & K S Kendler

  5. Department of Psychology, University of Florida, Gainesville, FL, USA

    D A Kertes

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Correspondence to M A Reimers.

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Reimers, M., Riley, B., Kalsi, G. et al. Pathway based analysis of genotypes in relation to alcohol dependence. Pharmacogenomics J 12, 342–348 (2012). https://doi.org/10.1038/tpj.2011.10

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