IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-49109-z.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-49109-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-49109-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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. 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.
    4. 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.
    5. 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.
    6. 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.
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Marta Alcalde-Herraiz & JunQing Xie & Danielle Newby & Clara Prats & Dipender Gill & María Gordillo-Marañón & Daniel Prieto-Alhambra & Martí Català & Albert Prats-Uribe, 2024. "Effect of genetically predicted sclerostin on cardiovascular biomarkers, risk factors, and disease outcomes," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Jingning Zhang & Jianan Zhan & Jin Jin & Cheng Ma & Ruzhang Zhao & Jared O’Connell & Yunxuan Jiang & Bertram L. Koelsch & Haoyu Zhang & Nilanjan Chatterjee, 2024. "An ensemble penalized regression method for multi-ancestry polygenic risk prediction," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Wenhan Chen & Yang Wu & Zhili Zheng & Ting Qi & Peter M. Visscher & Zhihong Zhu & Jian Yang, 2021. "Improved analyses of GWAS summary statistics by reducing data heterogeneity and errors," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    4. Danielle Rasooly & Gina M. Peloso & Alexandre C. Pereira & Hesam Dashti & Claudia Giambartolomei & Eleanor Wheeler & Nay Aung & Brian R. Ferolito & Maik Pietzner & Eric H. Farber-Eger & Quinn Stanton , 2023. "Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Jacob Joseph & Chang Liu & Qin Hui & Krishna Aragam & Zeyuan Wang & Brian Charest & Jennifer E. Huffman & Jacob M. Keaton & Todd L. Edwards & Serkalem Demissie & Luc Djousse & Juan P. Casas & J. Micha, 2022. "Genetic architecture of heart failure with preserved versus reduced ejection fraction," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    6. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Marco Lopez-Cruz & Fernando M. Aguate & Jacob D. Washburn & Natalia Leon & Shawn M. Kaeppler & Dayane Cristina Lima & Ruijuan Tan & Addie Thompson & Laurence Willard Bretonne & Gustavo los Campos, 2023. "Leveraging data from the Genomes-to-Fields Initiative to investigate genotype-by-environment interactions in maize in North America," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    8. Zhaotong Lin & Wei Pan, 2024. "A robust cis-Mendelian randomization method with application to drug target discovery," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    9. Beatrix Eugster & Rafael Lalive & Andreas Steinhauer & Josef Zweimüller, 2011. "The Demand for Social Insurance: Does Culture Matter?," Economic Journal, Royal Economic Society, vol. 121(556), pages 413-448, November.
    10. Michael G. Levin & Noah L. Tsao & Pankhuri Singhal & Chang Liu & Ha My T. Vy & Ishan Paranjpe & Joshua D. Backman & Tiffany R. Bellomo & William P. Bone & Kiran J. Biddinger & Qin Hui & Ozan Dikilitas, 2022. "Genome-wide association and multi-trait analyses characterize the common genetic architecture of heart failure," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    11. Filippini, Massimo & Wekhof, Tobias, 2021. "The effect of culture on energy efficient vehicle ownership," Journal of Environmental Economics and Management, Elsevier, vol. 105(C).
    12. Andrey V Khrunin & Denis V Khokhrin & Irina N Filippova & Tõnu Esko & Mari Nelis & Natalia A Bebyakova & Natalia L Bolotova & Janis Klovins & Liene Nikitina-Zake & Karola Rehnström & Samuli Ripatti & , 2013. "A Genome-Wide Analysis of Populations from European Russia Reveals a New Pole of Genetic Diversity in Northern Europe," PLOS ONE, Public Library of Science, vol. 8(3), pages 1-9, March.
    13. Pierre Luisi & Angelina García & Juan Manuel Berros & Josefina M B Motti & Darío A Demarchi & Emma Alfaro & Eliana Aquilano & Carina Argüelles & Sergio Avena & Graciela Bailliet & Julieta Beltramo & C, 2020. "Fine-scale genomic analyses of admixed individuals reveal unrecognized genetic ancestry components in Argentina," PLOS ONE, Public Library of Science, vol. 15(7), pages 1-30, July.
    14. Brielin C Brown & Nicolas L Bray & Lior Pachter, 2018. "Expression reflects population structure," PLOS Genetics, Public Library of Science, vol. 14(12), pages 1-15, December.
    15. Gad Abraham & Michael Inouye, 2014. "Fast Principal Component Analysis of Large-Scale Genome-Wide Data," PLOS ONE, Public Library of Science, vol. 9(4), pages 1-5, April.
    16. Beatrix Brügger & Rafael Lalive & Josef Zweimüller, 2009. "Does Culture Affect Unemployment? Evidence from the Röstigraben," NRN working papers 2009-10, The Austrian Center for Labor Economics and the Analysis of the Welfare State, Johannes Kepler University Linz, Austria.
    17. Diana Chang & Alon Keinan, 2014. "Principal Component Analysis Characterizes Shared Pathogenetics from Genome-Wide Association Studies," PLOS Computational Biology, Public Library of Science, vol. 10(9), pages 1-14, September.
    18. Alejandro Ochoa & John D Storey, 2021. "Estimating FST and kinship for arbitrary population structures," PLOS Genetics, Public Library of Science, vol. 17(1), pages 1-36, January.
    19. Victor Ronda & Esben Agerbo & Dorthe Bleses & Preben Bo Mortensen & Anders Børglum & Ole Mors & Michael Rosholm & David M. Hougaard & Merete Nordentoft & Thomas Werge, 2022. "Family disadvantage, gender, and the returns to genetic human capital," Scandinavian Journal of Economics, Wiley Blackwell, vol. 124(2), pages 550-578, April.
    20. Feldman, Michael J., 2023. "Spiked singular values and vectors under extreme aspect ratios," Journal of Multivariate Analysis, Elsevier, vol. 196(C).

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49109-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.