Investigating pleiotropic effects of statins on ischemic heart disease in the UK Biobank using Mendelian Randomization

  1. C M Schooling  Is a corresponding author
  2. J V Zhao
  3. S L Au Yeung
  4. G M Leung
  1. The University of Hong Kong, China

Abstract

We examined whether specifically statins, of the major lipid modifiers (statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe) have pleiotropic effects on ischemic heart disease (IHD) via testosterone in men or women. As a validation, we similarly assessed whether a drug that unexpectedly likely increases IHD also operates via testosterone. Using previously published genetic instruments we conducted a sex-specific univariable and multivariable Mendelian randomization study in the UK Biobank, including 179918 men with 25410 IHD cases and 212080 women with 12511 IHD cases. Of these three lipid modifiers, only genetically mimicking the effects of statins in men affected testosterone, which partly mediated effects on IHD. Correspondingly, genetically mimicking effects of anakinra on testosterone and IHD presented a reverse pattern to that for statins. These insights may facilitate the development of new interventions for cardiovascular diseases as well as highlighting the importance of sex-specific explanations, investigations, prevention and treatment.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. C M Schooling

    School of Public Health, The University of Hong Kong, Hong Kong, China
    For correspondence
    cms1@hku.hk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9933-5887
  2. J V Zhao

    School of Public Health, The University of Hong Kong, Hong Kong, China
    Competing interests
    The authors declare that no competing interests exist.
  3. S L Au Yeung

    School of Public Health, The University of Hong Kong, Hong Kong, China
    Competing interests
    The authors declare that no competing interests exist.
  4. G M Leung

    School of Public Health, The University of Hong Kong, Hong Kong, China
    Competing interests
    The authors declare that no competing interests exist.

Funding

The authors declare that there was no funding for this work

Ethics

Human subjects: This study is analysis of summary data previously collected with full consent

Reviewing Editor

  1. Edward D Janus, University of Melbourne, Australia

Version history

  1. Received: May 4, 2020
  2. Accepted: August 13, 2020
  3. Accepted Manuscript published: August 25, 2020 (version 1)
  4. Version of Record published: August 26, 2020 (version 2)

Copyright

© 2020, Schooling et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. C M Schooling
  2. J V Zhao
  3. S L Au Yeung
  4. G M Leung
(2020)
Investigating pleiotropic effects of statins on ischemic heart disease in the UK Biobank using Mendelian Randomization
eLife 9:e58567.
https://doi.org/10.7554/eLife.58567

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https://doi.org/10.7554/eLife.58567

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