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Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis

Author

Listed:
  • Markus Scholz

    (University of Leipzig
    University of Leipzig)

  • Katrin Horn

    (University of Leipzig
    University of Leipzig)

  • Janne Pott

    (University of Leipzig
    University of Leipzig)

  • Arnd Gross

    (University of Leipzig)

  • Marcus E. Kleber

    (Heidelberg University)

  • Graciela E. Delgado

    (Heidelberg University)

  • Pashupati Prasad Mishra

    (Tampere University)

  • Holger Kirsten

    (University of Leipzig
    University of Leipzig)

  • Christian Gieger

    (Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Center for Diabetes Research (DZD))

  • Martina Müller-Nurasyid

    (Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
    Ludwig-Maximilians University of Munich
    University Medical Center, Johannes Gutenberg University
    Hospital of the Ludwig-Maximilians-University Munich)

  • Anke Tönjes

    (University Hospital Leipzig)

  • Peter Kovacs

    (German Center for Diabetes Research (DZD)
    University Hospital Leipzig)

  • Terho Lehtimäki

    (Tampere University)

  • Olli Raitakari

    (Tampere University)

  • Mika Kähönen

    (Tampere University)

  • Helena Gylling

    (University of Helsinki and Helsinki University Hospital)

  • Ronny Baber

    (University of Leipzig
    University Hospital Leipzig)

  • Berend Isermann

    (University Hospital Leipzig)

  • Michael Stumvoll

    (University Hospital Leipzig)

  • Markus Loeffler

    (University of Leipzig
    University of Leipzig)

  • Winfried März

    (Heidelberg University
    Synlab Academy, Synlab Holding Deutschland GmbH
    Medical University Graz)

  • Thomas Meitinger

    (Technical University of Munich)

  • Annette Peters

    (Institue of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Joachim Thiery

    (University of Leipzig
    University Hospital Leipzig)

  • Daniel Teupser

    (Ludwig-Maximilians University of Munich)

  • Uta Ceglarek

    (University of Leipzig
    University Hospital Leipzig)

Abstract

Phytosterol serum concentrations are under tight genetic control. The relationship between phytosterols and coronary artery disease (CAD) is controversially discussed. We perform a genome-wide meta-analysis of 32 phytosterol traits reflecting resorption, cholesterol synthesis and esterification in six studies with up to 9758 subjects and detect ten independent genome-wide significant SNPs at seven genomic loci. We confirm previously established associations at ABCG5/8 and ABO and demonstrate an extended locus heterogeneity at ABCG5/8 with different functional mechanisms. New loci comprise HMGCR, NPC1L1, PNLIPRP2, SCARB1 and APOE. Based on these results, we perform Mendelian Randomization analyses (MR) revealing a risk-increasing causal relationship of sitosterol serum concentrations and CAD, which is partly mediated by cholesterol. Here we report that phytosterols are polygenic traits. MR add evidence of both, direct and indirect causal effects of sitosterol on CAD.

Suggested Citation

  • Markus Scholz & Katrin Horn & Janne Pott & Arnd Gross & Marcus E. Kleber & Graciela E. Delgado & Pashupati Prasad Mishra & Holger Kirsten & Christian Gieger & Martina Müller-Nurasyid & Anke Tönjes & P, 2022. "Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27706-6
    DOI: 10.1038/s41467-021-27706-6
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    Cited by:

    1. Markus Scholz & Katrin Horn & Janne Pott & Matthias Wuttke & Andreas Kühnapfel & M. Kamal Nasr & Holger Kirsten & Yong Li & Anselm Hoppmann & Mathias Gorski & Sahar Ghasemi & Man Li & Adrienne Tin & J, 2024. "X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response element," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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