1. Epidemiology and Global Health
  2. Evolutionary Biology
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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
Research Article
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Cite this article as: eLife 2020;9:e58567 doi: 10.7554/eLife.58567


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.

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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
    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.


The authors declare that there was no funding for this work


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

Reviewing Editor

  1. Edward D Janus, University of Melbourne, Australia

Publication 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)


© 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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Further reading

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    2. Microbiology and Infectious Disease
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    Respiratory protective equipment recommended in the UK for healthcare workers (HCWs) caring for patients with COVID-19 comprises a fluid-resistant surgical mask (FRSM), except in the context of aerosol generating procedures (AGPs). We previously demonstrated frequent pauci- and asymptomatic severe acute respiratory syndrome coronavirus 2 infection HCWs during the first wave of the COVID-19 pandemic in the UK, using a comprehensive PCR-based HCW screening programme (Rivett et al., 2020; Jones et al., 2020).


    Here, we use observational data and mathematical modelling to analyse infection rates amongst HCWs working on ‘red’ (coronavirus disease 2019, COVID-19) and ‘green’ (non-COVID-19) wards during the second wave of the pandemic, before and after the substitution of filtering face piece 3 (FFP3) respirators for FRSMs.


    Whilst using FRSMs, HCWs working on red wards faced an approximately 31-fold (and at least fivefold) increased risk of direct, ward-based infection. Conversely, after changing to FFP3 respirators, this risk was significantly reduced (52–100% protection).


    FFP3 respirators may therefore provide more effective protection than FRSMs for HCWs caring for patients with COVID-19, whether or not AGPs are undertaken.


    Wellcome Trust, Medical Research Council, Addenbrooke’s Charitable Trust, NIHR Cambridge Biomedical Research Centre, NHS Blood and Transfusion, UKRI.

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    Methods: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings.

    Results: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, with low-income settings characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made.

    Conclusions: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions.

    Funding: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).