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Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases

Author

Listed:
  • Adrien Georges

    (PARCC, INSERM, Université de Paris)

  • Min-Lee Yang

    (University of Michigan Medical School
    University of Michigan Medical School)

  • Takiy-Eddine Berrandou

    (PARCC, INSERM, Université de Paris)

  • Mark K. Bakker

    (University Medical Center Utrecht Brain Center, Utrecht University)

  • Ozan Dikilitas

    (Mayo Clinic)

  • Soto Romuald Kiando

    (PARCC, INSERM, Université de Paris)

  • Lijiang Ma

    (Icahn School of Medicine at Mount Sinai)

  • Benjamin A. Satterfield

    (Mayo Clinic)

  • Sebanti Sengupta

    (University of Michigan Medical School)

  • Mengyao Yu

    (PARCC, INSERM, Université de Paris)

  • Jean-François Deleuze

    (CEA and Fondation Jean Dausset-CEPH)

  • Delia Dupré

    (PARCC, INSERM, Université de Paris)

  • Kristina L. Hunker

    (University of Michigan Medical School
    University of Michigan Medical School)

  • Sergiy Kyryachenko

    (PARCC, INSERM, Université de Paris)

  • Lu Liu

    (PARCC, INSERM, Université de Paris)

  • Ines Sayoud-Sadeg

    (PARCC, INSERM, Université de Paris)

  • Laurence Amar

    (PARCC, INSERM, Université de Paris
    Hôpital Européen Georges Pompidou)

  • Chad M. Brummett

    (University of Michigan)

  • Dawn M. Coleman

    (University of Michigan)

  • Valentina d’Escamard

    (Icahn School of Medicine at Mount Sinai)

  • Peter de Leeuw

    (Section Vascular Medicine, Maastricht University Medical Centre, Maastricht University
    Maastricht University Medical Centre, Maastricht University)

  • Natalia Fendrikova-Mahlay

    (Cleveland Clinic)

  • Daniella Kadian-Dodov

    (Kravis Center for Cardiovascular Health Icahn School of Medicine at Mount Sinai)

  • Jun Z. Li

    (University of Michigan Medical School)

  • Aurélien Lorthioir

    (PARCC, INSERM, Université de Paris
    Hôpital Européen Georges Pompidou)

  • Marco Pappaccogli

    (Université Catholique de Louvain
    University of Turin)

  • Aleksander Prejbisz

    (National Institute of Cardiology)

  • Witold Smigielski

    (University of Lodz)

  • James C. Stanley

    (University of Michigan)

  • Matthew Zawistowski

    (University of Michigan School of Public Health)

  • Xiang Zhou

    (University of Michigan School of Public Health)

  • Sebastian Zöllner

    (University of Michigan School of Public Health)

  • Philippe Amouyel

    (Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE - Labex DISTALZ - Risk factors and molecular determinants of aging-related disease)

  • Marc L. De Buyzere

    (Ghent University and Ghent University Hospital)

  • Stéphanie Debette

    (Bordeaux University Hospital, Inserm U1219)

  • Piotr Dobrowolski

    (National Institute of Cardiology)

  • Wojciech Drygas

    (National Institute of Cardiology)

  • Heather L. Gornik

    (Cleveland Clinic)

  • Jeffrey W. Olin

    (Kravis Center for Cardiovascular Health Icahn School of Medicine at Mount Sinai)

  • Jerzy Piwonski

    (National Institute of Cardiology)

  • Ernst R. Rietzschel

    (Ghent University and Ghent University Hospital)

  • Ynte M. Ruigrok

    (Mayo Clinic)

  • Miikka Vikkula

    (Université Catholique de Louvain)

  • Ewa Warchol Celinska

    (National Institute of Cardiology)

  • Andrzej Januszewicz

    (National Institute of Cardiology)

  • Iftikhar J. Kullo

    (Mayo Clinic
    Mayo Clinic)

  • Michel Azizi

    (Hôpital Européen Georges Pompidou
    Université de Paris, Inserm)

  • Xavier Jeunemaitre

    (PARCC, INSERM, Université de Paris
    Hôpital Européen Georges Pompidou)

  • Alexandre Persu

    (Université Catholique de Louvain
    Université Catholique de Louvain)

  • Jason C. Kovacic

    (Kravis Center for Cardiovascular Health Icahn School of Medicine at Mount Sinai
    Victor Chang Cardiac Research Institute
    University of New South Wales)

  • Santhi K. Ganesh

    (University of Michigan Medical School
    University of Michigan Medical School)

  • Nabila Bouatia-Naji

    (PARCC, INSERM, Université de Paris)

Abstract

Fibromuscular dysplasia (FMD) is an arteriopathy associated with hypertension, stroke and myocardial infarction, affecting mostly women. We report results from the first genome-wide association meta-analysis of six studies including 1556 FMD cases and 7100 controls. We find an estimate of SNP-based heritability compatible with FMD having a polygenic basis, and report four robustly associated loci (PHACTR1, LRP1, ATP2B1, and LIMA1). Transcriptome-wide association analysis in arteries identifies one additional locus (SLC24A3). We characterize open chromatin in arterial primary cells and find that FMD associated variants are located in arterial-specific regulatory elements. Target genes are broadly involved in mechanisms related to actin cytoskeleton and intracellular calcium homeostasis, central to vascular contraction. We find significant genetic overlap between FMD and more common cardiovascular diseases and traits including blood pressure, migraine, intracranial aneurysm, and coronary artery disease.

Suggested Citation

  • Adrien Georges & Min-Lee Yang & Takiy-Eddine Berrandou & Mark K. Bakker & Ozan Dikilitas & Soto Romuald Kiando & Lijiang Ma & Benjamin A. Satterfield & Sebanti Sengupta & Mengyao Yu & Jean-François De, 2021. "Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26174-2
    DOI: 10.1038/s41467-021-26174-2
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    References listed on IDEAS

    as
    1. Caryn S. Ross-Innes & Rory Stark & Andrew E. Teschendorff & Kelly A. Holmes & H. Raza Ali & Mark J. Dunning & Gordon D. Brown & Ondrej Gojis & Ian O. Ellis & Andrew R. Green & Simak Ali & Suet-Feung C, 2012. "Differential oestrogen receptor binding is associated with clinical outcome in breast cancer," Nature, Nature, vol. 481(7381), pages 389-393, January.
    2. 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.
    3. Zhihong Zhu & Zhili Zheng & Futao Zhang & Yang Wu & Maciej Trzaskowski & Robert Maier & Matthew R. Robinson & John J. McGrath & Peter M. Visscher & Naomi R. Wray & Jian Yang, 2018. "Causal associations between risk factors and common diseases inferred from GWAS summary data," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
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