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Accounting for Non-genetic Factors Improves the Power of eQTL Studies

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Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 4955))

Abstract

The recent availability of large scale data sets profiling single nucleotide polymorphisms (SNPs) and gene expression across different human populations, has directed much attention towards discovering patterns of genetic variation and their association with gene regulation. The influence of environmental, developmental and other factors on gene expression can obscure such associations. We present a model that explicitly accounts for non-genetic factors so as to improve significantly the power of an expression Quantitative Trait Loci (eQTL) study. Our method also exploits the inherent block structure of haplotype data to further enhance its sensitivity. On data from the HapMap project, we find more than three times as many significant associations than a standard eQTL method.

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References

  1. Kendziorski, C.M., Chen, M., Yuan, M., Lan, H., Attie, A.D.: Statistical methods for expression quantitative trait loci (eQTL) mapping. Biometrics 62(1), 19–27 (2006)

    Article  MathSciNet  MATH  Google Scholar 

  2. Brem, R.B., Kruglyak, L.: The landscape of genetic complexity across 5,700 gene expression traits in yeast. Proc. Natl. Acad. Sci. 102(5), 1572–1577 (2005)

    Article  Google Scholar 

  3. Huang, J., Kannan, A., Winn, J.: Bayesian association of haplotypes and non-genetic factors to regulatory and phenotypic variation in human populations. Bioinformatics 23(13), i212–i221 (2007)

    Article  Google Scholar 

  4. The International HapMap Consortium: A haplotype map of the human genome. Nature 437, 1299–1320 (2005)

    Google Scholar 

  5. Roweis, S.T., Ghahramani, Z.: A unifying review of linear Gaussian models. Neural Computation 11(2), 305–345 (1999)

    Article  Google Scholar 

  6. Tipping, M.E., Bishop, C.M.: Probabilistic principal component analysis. Journal of the Royal Statistical Society, Series B 21(3), 611–622 (1999)

    MathSciNet  Google Scholar 

  7. Liebermeister, W.: Linear modes of gene expression determined by independent component analysis. Bioinformatics 18(1), 51–60 (2002)

    Article  Google Scholar 

  8. Iosifina, P., Lorenz, W.: Factor analysis for gene regulatory networks and transcription factor activity profiles. BMC Bioinformatics

    Google Scholar 

  9. Lan, H., Stoehr, J.P., Nadler, S.T., Schueler, K., Yandell, B., Attie, A.D.: Dimension reduction for mapping mRNA abundance as quantitative traits. Genetics 121, 1607–1614 (2003)

    Google Scholar 

  10. Hastie, T., Tibshirani, R., Eisen, A., Levy, R., Staudt, L., Chan, D., Brown, P.: Gene shaving as a method for identifying distinct sets of genes with similar expression patterns. Genome Biology (2000)

    Google Scholar 

  11. Bishop, C.M.: Bayesian PCA. Advances in Neural Information Processing Systems 11, 382–388 (1999)

    Google Scholar 

  12. Stranger, B., Forrest, M., Dunning, M., Ingle, C., Beazley, C., et al.: Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315, 848–853 (2007)

    Article  Google Scholar 

  13. Bishop, C.M., Winn, J., Spiegelhalter, D.: VIBES: A variational inference engine for Bayesian networks. In: Advances in Neural Information Processing Systems, vol. 15, pp. 793–800 (2002)

    Google Scholar 

  14. Lander, E., Botstein, D.: Mapping Mendelian Factors Underlying Quantitative Traits Using RFLP Linkage Maps. Genetics 121(1), 185–199 (1989)

    Google Scholar 

  15. Kamisetty, H., Kannan, A., Winn, J.: A Bayesian model for population-stratified haplotype block inference, http://research.microsoft.com/mlp/bio/piSNP.html

  16. Kummerfeld, S., Teichmann, S.: DBD: a transcription factor prediction database. Nucleic Acids Res. 34(Database issue), D74–D81 (2006)

    Article  Google Scholar 

  17. Sen, S., Churchill, G.A.: A statistical framework for quantitative trait mapping. Genetics 159, 371–387 (2001)

    Google Scholar 

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Martin Vingron Limsoon Wong

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© 2008 Springer-Verlag Berlin Heidelberg

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Stegle, O., Kannan, A., Durbin, R., Winn, J. (2008). Accounting for Non-genetic Factors Improves the Power of eQTL Studies. In: Vingron, M., Wong, L. (eds) Research in Computational Molecular Biology. RECOMB 2008. Lecture Notes in Computer Science(), vol 4955. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-78839-3_35

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  • DOI: https://doi.org/10.1007/978-3-540-78839-3_35

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-78838-6

  • Online ISBN: 978-3-540-78839-3

  • eBook Packages: Computer ScienceComputer Science (R0)

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