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

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 Deleuze, Delia Dupré, Kristina L. Hunker, Sergiy Kyryachenko, Lu Liu, Ines Sayoud-Sadeg, Laurence Amar, Chad M. Brummett, Dawn M. Coleman, Valentina d’Escamard, Peter de Leeuw, Natalia Fendrikova-Mahlay, Daniella Kadian-Dodov, Jun Z. Li, Aurélien Lorthioir, Marco Pappaccogli, Aleksander Prejbisz, Witold Smigielski, James C. Stanley, Matthew Zawistowski, Xiang Zhou, Sebastian Zöllner, Philippe Amouyel, Marc L. De Buyzere, Stéphanie Debette, Piotr Dobrowolski, Wojciech Drygas, Heather L. Gornik, Jeffrey W. Olin, Jerzy Piwonski, Ernst R. Rietzschel, Ynte M. Ruigrok, Miikka Vikkula, Ewa Warchol Celinska, Andrzej Januszewicz, Iftikhar J. Kullo, Michel Azizi, Xavier Jeunemaitre, Alexandre Persu, Jason C. Kovacic, Santhi K. Ganesh () and Nabila Bouatia-Naji ()
Additional contact information
Adrien Georges: PARCC, INSERM, Université de Paris
Min-Lee Yang: 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
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
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
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
Marco Pappaccogli: Université Catholique de Louvain
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
Michel Azizi: Hôpital Européen Georges Pompidou
Xavier Jeunemaitre: PARCC, INSERM, Université de Paris
Alexandre Persu: Université Catholique de Louvain
Jason C. Kovacic: Kravis Center for Cardiovascular Health Icahn School of Medicine at Mount Sinai
Santhi K. Ganesh: University of Michigan Medical School
Nabila Bouatia-Naji: PARCC, INSERM, Université de Paris

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-26174-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26174-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-26174-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().