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

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...

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Autores principales: Georges, Adrien, Yang, Min-Lee, Berrandou, Takiy-Eddine, Bakker, Mark K., Dikilitas, Ozan, Kiando, Soto Romuald, Ma, Lijiang, Satterfield, Benjamin A., Sengupta, Sebanti, Yu, Mengyao, Deleuze, Jean-François, Dupré, Delia, Hunker, Kristina L., Kyryachenko, Sergiy, Liu, Lu, Sayoud-Sadeg, Ines, Amar, Laurence, Brummett, Chad M., Coleman, Dawn M., d’Escamard, Valentina, de Leeuw, Peter, Fendrikova-Mahlay, Natalia, Kadian-Dodov, Daniella, Li, Jun Z., Lorthioir, Aurélien, Pappaccogli, Marco, Prejbisz, Aleksander, Smigielski, Witold, Stanley, James C., Zawistowski, Matthew, Zhou, Xiang, Zöllner, Sebastian, Amouyel, Philippe, De Buyzere, Marc L., Debette, Stéphanie, Dobrowolski, Piotr, Drygas, Wojciech, Gornik, Heather L., Olin, Jeffrey W., Piwonski, Jerzy, Rietzschel, Ernst R., Ruigrok, Ynte M., Vikkula, Miikka, Warchol Celinska, Ewa, Januszewicz, Andrzej, Kullo, Iftikhar J., Azizi, Michel, Jeunemaitre, Xavier, Persu, Alexandre, Kovacic, Jason C., Ganesh, Santhi K., Bouatia-Naji, Nabila
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521585/
https://www.ncbi.nlm.nih.gov/pubmed/34654805
http://dx.doi.org/10.1038/s41467-021-26174-2
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author Georges, Adrien
Yang, Min-Lee
Berrandou, Takiy-Eddine
Bakker, Mark K.
Dikilitas, Ozan
Kiando, Soto Romuald
Ma, Lijiang
Satterfield, Benjamin A.
Sengupta, Sebanti
Yu, Mengyao
Deleuze, Jean-François
Dupré, Delia
Hunker, Kristina L.
Kyryachenko, Sergiy
Liu, Lu
Sayoud-Sadeg, Ines
Amar, Laurence
Brummett, Chad M.
Coleman, Dawn M.
d’Escamard, Valentina
de Leeuw, Peter
Fendrikova-Mahlay, Natalia
Kadian-Dodov, Daniella
Li, Jun Z.
Lorthioir, Aurélien
Pappaccogli, Marco
Prejbisz, Aleksander
Smigielski, Witold
Stanley, James C.
Zawistowski, Matthew
Zhou, Xiang
Zöllner, Sebastian
Amouyel, Philippe
De Buyzere, Marc L.
Debette, Stéphanie
Dobrowolski, Piotr
Drygas, Wojciech
Gornik, Heather L.
Olin, Jeffrey W.
Piwonski, Jerzy
Rietzschel, Ernst R.
Ruigrok, Ynte M.
Vikkula, Miikka
Warchol Celinska, Ewa
Januszewicz, Andrzej
Kullo, Iftikhar J.
Azizi, Michel
Jeunemaitre, Xavier
Persu, Alexandre
Kovacic, Jason C.
Ganesh, Santhi K.
Bouatia-Naji, Nabila
author_facet Georges, Adrien
Yang, Min-Lee
Berrandou, Takiy-Eddine
Bakker, Mark K.
Dikilitas, Ozan
Kiando, Soto Romuald
Ma, Lijiang
Satterfield, Benjamin A.
Sengupta, Sebanti
Yu, Mengyao
Deleuze, Jean-François
Dupré, Delia
Hunker, Kristina L.
Kyryachenko, Sergiy
Liu, Lu
Sayoud-Sadeg, Ines
Amar, Laurence
Brummett, Chad M.
Coleman, Dawn M.
d’Escamard, Valentina
de Leeuw, Peter
Fendrikova-Mahlay, Natalia
Kadian-Dodov, Daniella
Li, Jun Z.
Lorthioir, Aurélien
Pappaccogli, Marco
Prejbisz, Aleksander
Smigielski, Witold
Stanley, James C.
Zawistowski, Matthew
Zhou, Xiang
Zöllner, Sebastian
Amouyel, Philippe
De Buyzere, Marc L.
Debette, Stéphanie
Dobrowolski, Piotr
Drygas, Wojciech
Gornik, Heather L.
Olin, Jeffrey W.
Piwonski, Jerzy
Rietzschel, Ernst R.
Ruigrok, Ynte M.
Vikkula, Miikka
Warchol Celinska, Ewa
Januszewicz, Andrzej
Kullo, Iftikhar J.
Azizi, Michel
Jeunemaitre, Xavier
Persu, Alexandre
Kovacic, Jason C.
Ganesh, Santhi K.
Bouatia-Naji, Nabila
author_sort Georges, Adrien
collection PubMed
description 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.
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spelling pubmed-85215852021-10-29 Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases Georges, Adrien Yang, Min-Lee Berrandou, Takiy-Eddine Bakker, Mark K. Dikilitas, Ozan Kiando, Soto Romuald Ma, Lijiang Satterfield, Benjamin A. Sengupta, Sebanti Yu, Mengyao Deleuze, Jean-François Dupré, Delia Hunker, Kristina L. Kyryachenko, Sergiy Liu, Lu Sayoud-Sadeg, Ines Amar, Laurence Brummett, Chad M. Coleman, Dawn M. d’Escamard, Valentina de Leeuw, Peter Fendrikova-Mahlay, Natalia Kadian-Dodov, Daniella Li, Jun Z. Lorthioir, Aurélien Pappaccogli, Marco Prejbisz, Aleksander Smigielski, Witold Stanley, James C. Zawistowski, Matthew Zhou, Xiang Zöllner, Sebastian Amouyel, Philippe De Buyzere, Marc L. Debette, Stéphanie Dobrowolski, Piotr Drygas, Wojciech Gornik, Heather L. Olin, Jeffrey W. Piwonski, Jerzy Rietzschel, Ernst R. Ruigrok, Ynte M. Vikkula, Miikka Warchol Celinska, Ewa Januszewicz, Andrzej Kullo, Iftikhar J. Azizi, Michel Jeunemaitre, Xavier Persu, Alexandre Kovacic, Jason C. Ganesh, Santhi K. Bouatia-Naji, Nabila Nat Commun Article 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. Nature Publishing Group UK 2021-10-15 /pmc/articles/PMC8521585/ /pubmed/34654805 http://dx.doi.org/10.1038/s41467-021-26174-2 Text en © The Author(s) 2021, corrected publication 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Georges, Adrien
Yang, Min-Lee
Berrandou, Takiy-Eddine
Bakker, Mark K.
Dikilitas, Ozan
Kiando, Soto Romuald
Ma, Lijiang
Satterfield, Benjamin A.
Sengupta, Sebanti
Yu, Mengyao
Deleuze, Jean-François
Dupré, Delia
Hunker, Kristina L.
Kyryachenko, Sergiy
Liu, Lu
Sayoud-Sadeg, Ines
Amar, Laurence
Brummett, Chad M.
Coleman, Dawn M.
d’Escamard, Valentina
de Leeuw, Peter
Fendrikova-Mahlay, Natalia
Kadian-Dodov, Daniella
Li, Jun Z.
Lorthioir, Aurélien
Pappaccogli, Marco
Prejbisz, Aleksander
Smigielski, Witold
Stanley, James C.
Zawistowski, Matthew
Zhou, Xiang
Zöllner, Sebastian
Amouyel, Philippe
De Buyzere, Marc L.
Debette, Stéphanie
Dobrowolski, Piotr
Drygas, Wojciech
Gornik, Heather L.
Olin, Jeffrey W.
Piwonski, Jerzy
Rietzschel, Ernst R.
Ruigrok, Ynte M.
Vikkula, Miikka
Warchol Celinska, Ewa
Januszewicz, Andrzej
Kullo, Iftikhar J.
Azizi, Michel
Jeunemaitre, Xavier
Persu, Alexandre
Kovacic, Jason C.
Ganesh, Santhi K.
Bouatia-Naji, Nabila
Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases
title Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases
title_full Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases
title_fullStr Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases
title_full_unstemmed Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases
title_short Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases
title_sort genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521585/
https://www.ncbi.nlm.nih.gov/pubmed/34654805
http://dx.doi.org/10.1038/s41467-021-26174-2
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