Sex-biased genetic effects on gene regulation in humans

  1. Emmanouil T. Dermitzakis1,9
  1. 1Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva 1211, Switzerland;
  2. 2Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom;
  3. 3Biomedical Sciences Research Center Al. Fleming, 16672 Vari, Greece;
  4. 4Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA;
  5. 5Harvard Medical School, Boston, Massachusetts 02115, USA;
  6. 6Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA;
  7. 7Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom;
  8. 8Oxford NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom

    Abstract

    Human regulatory variation, reported as expression quantitative trait loci (eQTLs), contributes to differences between populations and tissues. The contribution of eQTLs to differences between sexes, however, has not been investigated to date. Here we explore regulatory variation in females and males and demonstrate that 12%–15% of autosomal eQTLs function in a sex-biased manner. We show that genes possessing sex-biased eQTLs are expressed at similar levels across the sexes and highlight cases of genes controlling sexually dimorphic and shared traits that are under the control of distinct regulatory elements in females and males. This study illustrates that sex provides important context that can modify the effects of functional genetic variants.

    Footnotes

    • 9 Corresponding author

      E-mail emmanouil.dermitzakis{at}unige.ch

    • [Supplemental material is available for this article.]

    • Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.134981.111.

      Freely available online through the Genome Research Open Access option.

    • Received November 17, 2011.
    • Accepted August 13, 2012.

    This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.

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