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Comparing the effects of CETP in East Asian and European ancestries: a Mendelian randomization study

Author

Listed:
  • Diana Dunca

    (University College London
    University College London)

  • Sandesh Chopade

    (University College London)

  • María Gordillo-Marañón

    (University College London)

  • Aroon D. Hingorani

    (University College London
    UCL British Heart Foundation Research Accelerator
    Health Data Research UK)

  • Karoline Kuchenbaecker

    (University College London
    University College London)

  • Chris Finan

    (University College London
    UCL British Heart Foundation Research Accelerator
    Health Data Research UK)

  • Amand F. Schmidt

    (University College London
    UCL British Heart Foundation Research Accelerator
    Amsterdam UMC Heart Center)

Abstract

CETP inhibitors are a class of lipid-lowering drugs in development for treatment of coronary heart disease (CHD). Genetic studies in East Asian ancestry have interpreted the lack of CETP signal with low-density lipoprotein cholesterol (LDL-C) and lack of drug target Mendelian randomization (MR) effect on CHD as evidence that CETP inhibitors might not be effective in East Asian participants. Capitalizing on recent increases in sample size of East Asian genetic studies, we conducted a drug target MR analysis, scaled to a standard deviation increase in high-density lipoprotein cholesterol. Despite finding evidence for possible neutral effects of lower CETP levels on LDL-C, systolic blood pressure and pulse pressure in East Asians (interaction p-values

Suggested Citation

  • Diana Dunca & Sandesh Chopade & María Gordillo-Marañón & Aroon D. Hingorani & Karoline Kuchenbaecker & Chris Finan & Amand F. Schmidt, 2024. "Comparing the effects of CETP in East Asian and European ancestries: a Mendelian randomization study," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49109-z
    DOI: 10.1038/s41467-024-49109-z
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    References listed on IDEAS

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    1. Claudia Giambartolomei & Damjan Vukcevic & Eric E Schadt & Lude Franke & Aroon D Hingorani & Chris Wallace & Vincent Plagnol, 2014. "Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics," PLOS Genetics, Public Library of Science, vol. 10(5), pages 1-15, May.
    2. Amand F. Schmidt & Chris Finan & Maria Gordillo-Marañón & Folkert W. Asselbergs & Daniel F. Freitag & Riyaz S. Patel & Benoît Tyl & Sandesh Chopade & Rupert Faraway & Magdalena Zwierzyna & Aroon D. Hi, 2020. "Genetic drug target validation using Mendelian randomisation," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    3. Amand F. Schmidt & Nicholas B. Hunt & Maria Gordillo-Marañón & Pimphen Charoen & Fotios Drenos & Mika Kivimaki & Deborah A. Lawlor & Claudia Giambartolomei & Olia Papacosta & Nishi Chaturvedi & Joshua, 2021. "Cholesteryl ester transfer protein (CETP) as a drug target for cardiovascular disease," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    4. John Novembre & Toby Johnson & Katarzyna Bryc & Zoltán Kutalik & Adam R. Boyko & Adam Auton & Amit Indap & Karen S. King & Sven Bergmann & Matthew R. Nelson & Matthew Stephens & Carlos D. Bustamante, 2008. "Genes mirror geography within Europe," Nature, Nature, vol. 456(7219), pages 274-274, November.
    5. Aniket Mishra & Rainer Malik & Tsuyoshi Hachiya & Tuuli Jürgenson & Shinichi Namba & Daniel C. Posner & Frederick K. Kamanu & Masaru Koido & Quentin Le Grand & Mingyang Shi & Yunye He & Marios K. Geor, 2022. "Stroke genetics informs drug discovery and risk prediction across ancestries," Nature, Nature, vol. 611(7934), pages 115-123, November.
    6. Christoph Nowak & Johan Ärnlöv, 2018. "A Mendelian randomization study of the effects of blood lipids on breast cancer risk," Nature Communications, Nature, vol. 9(1), pages 1-7, December.
    7. Sarah E. Graham & Shoa L. Clarke & Kuan-Han H. Wu & Stavroula Kanoni & Greg J. M. Zajac & Shweta Ramdas & Ida Surakka & Ioanna Ntalla & Sailaja Vedantam & Thomas W. Winkler & Adam E. Locke & Eirini Ma, 2021. "The power of genetic diversity in genome-wide association studies of lipids," Nature, Nature, vol. 600(7890), pages 675-679, December.
    8. Aniket Mishra & Rainer Malik & Tsuyoshi Hachiya & Tuuli Jürgenson & Shinichi Namba & Daniel C. Posner & Frederick K. Kamanu & Masaru Koido & Quentin Le Grand & Mingyang Shi & Yunye He & Marios K. Geor, 2022. "Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries," Nature, Nature, vol. 612(7938), pages 7-7, December.
    9. John Novembre & Toby Johnson & Katarzyna Bryc & Zoltán Kutalik & Adam R. Boyko & Adam Auton & Amit Indap & Karen S. King & Sven Bergmann & Matthew R. Nelson & Matthew Stephens & Carlos D. Bustamante, 2008. "Genes mirror geography within Europe," Nature, Nature, vol. 456(7218), pages 98-101, November.
    10. Sonia Shah & Albert Henry & Carolina Roselli & Honghuang Lin & Garðar Sveinbjörnsson & Ghazaleh Fatemifar & Åsa K. Hedman & Jemma B. Wilk & Michael P. Morley & Mark D. Chaffin & Anna Helgadottir & Nie, 2020. "Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
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