1. Genetics and Genomics
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A Mendelian randomization study of the role of lipoprotein subfractions in coronary artery disease

  1. Qingyuan Zhao  Is a corresponding author
  2. Jingshu Wang
  3. Zhen Miao
  4. Nancy R Zhang
  5. Sean Hennessy
  6. Dylan S Small
  7. Daniel J Rader
  1. University of Cambridge, United Kingdom
  2. University of Chicago, United States
  3. University of Pennsylvania, United States
Research Article
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Cite this article as: eLife 2021;10:e58361 doi: 10.7554/eLife.58361

Abstract

Recent genetic data can offer important insights into the roles of lipoprotein subfractions and particle sizes in preventing coronary artery disease (CAD), as previous observational studies have often reported conflicting results. We used the LD score regression to estimate the genetic correlation of 77 subfraction traits with traditional lipid profile and identified 27 traits that may represent distinct genetic mechanisms. We then used Mendelian randomization (MR) to estimate the causal effect of these traits on the risk of CAD. In univariable MR, the concentration and content of medium high-density lipoprotein (HDL) particles showed a protective effect against CAD. The effect was not attenuated in multivariable analyses. Multivariable MR analyses also found that small HDL particles and smaller mean HDL particle diameter may have a protective effect. We identified four genetic markers for HDL particle size and CAD. Further investigations are needed to fully understand the role of HDL particle size.

Data availability

GWAS data used in the data are publicly available. Details can be found in Table 1.

The following previously published data sets were used

Article and author information

Author details

  1. Qingyuan Zhao

    Statistical Laboratory, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    qyzhao@statslab.cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9902-2768
  2. Jingshu Wang

    Department of Statistics, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Zhen Miao

    Genomics and Computational Biology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3255-9517
  4. Nancy R Zhang

    Department of Statistics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sean Hennessy

    Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Dylan S Small

    Department of Statistics, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4928-2646
  7. Daniel J Rader

    Department of Medicine, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

No external funding was received for this work.

Reviewing Editor

  1. Edward D Janus, University of Melbourne, Australia

Publication history

  1. Received: April 28, 2020
  2. Accepted: April 23, 2021
  3. Accepted Manuscript published: April 26, 2021 (version 1)
  4. Version of Record published: May 28, 2021 (version 2)

Copyright

© 2021, Zhao 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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