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Expression QTLs Mapping and Analysis: A Bayesian Perspective

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Systems Genetics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1488))

Abstract

The aim of expression Quantitative Trait Locus (eQTL) mapping is the identification of DNA sequence variants that explain variation in gene expression. Given the recent yield of trait-associated genetic variants identified by large-scale genome-wide association analyses (GWAS), eQTL mapping has become a useful tool to understand the functional context where these variants operate and eventually narrow down functional gene targets for disease. Despite its extensive application to complex (polygenic) traits and disease, the majority of eQTL studies still rely on univariate data modeling strategies, i.e., testing for association of all transcript-marker pairs. However these “one at-a-time” strategies are (1) unable to control the number of false-positives when an intricate Linkage Disequilibrium structure is present and (2) are often underpowered to detect the full spectrum of trans-acting regulatory effects. Here we present our viewpoint on the most recent advances on eQTL mapping approaches, with a focus on Bayesian methodology. We review the advantages of the Bayesian approach over frequentist methods and provide an empirical example of polygenic eQTL mapping to illustrate the different properties of frequentist and Bayesian methods. Finally, we discuss how multivariate eQTL mapping approaches have distinctive features with respect to detection of polygenic effects, accuracy, and interpretability of the results.

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Acknowledgments

We acknowledge funding from Medical Research Council Grant G 1002319 (L.B.), MR/M013138/1 (L.B.), MR/M004716/1 (M.I. and E.P.) and Duke-NUS Graduate Medical School Singapore (E.P.).

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    Authors and Affiliations

    1. Centre for Complement and Inflammation Research, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK

      Martha Imprialou

    2. Department of Medical Genetics, University of Cambridge, Box 238, Lv 6 Addenbrooke’s Treatment Centre, Addenbrooke’s Hospital, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK

      Leonardo Bottolo

    3. Department of Mathematics, Imperial College London, 180 Queen’s Gate, London, SW7 2AZ, UK

      Leonardo Bottolo

    4. Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore

      Enrico Petretto

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    1. Martha Imprialou
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    Correspondence to Enrico Petretto or Leonardo Bottolo .

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    1. Department of Infection Genetics, Helmholtz Centre for Infection Research & University of Veterinary Medicine Hannover, Braunschweig, Niedersachsen, Germany

      Klaus Schughart

    2. Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA

      Robert W. Williams

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    Imprialou, M., Petretto, E., Bottolo, L. (2017). Expression QTLs Mapping and Analysis: A Bayesian Perspective. In: Schughart, K., Williams, R. (eds) Systems Genetics. Methods in Molecular Biology, vol 1488. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6427-7_8

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    • DOI: https://doi.org/10.1007/978-1-4939-6427-7_8

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