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

Author

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, FEIRI investigators, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, MEGASTROKE, 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

Subjects
Science
Abstract

Fibromuscular dysplasia is a cardiovascular disease affecting mostly women with a mostly unknown genetic basis. Here the authors have performed a genome-wide association meta-analysis of Fibromuscular dysplasia to identify genetic loci, some of which are shared with common cardiovascular disease and traits.

Published
2021
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2. Author Correction: Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases

Author

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, FEIRI investigators, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, MEGASTROKE, 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, ARCADIA Investigators, Xavier Jeunemaitre, Alexandre Persu, Jason C. Kovacic, Santhi K. Ganesh, and Nabila Bouatia-Naji

Subjects
Science
Published
2022
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3. Author Correction: Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases

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, FEIRI investigators, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, MEGASTROKE, 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, ARCADIA Investigators, Jeunemaitre, Xavier, Persu, Alexandre, Kovacic, Jason C, Ganesh, Santhi K, Bouatia-Naji, Nabila, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, and UCL - (SLuc) Département cardiovasculaire

Subjects
Multidisciplinary, General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology
Abstract

No abstract available

Published
2022

4. Author Correction: Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases.

Author

UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Département cardiovasculaire, 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, FEIRI investigators, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, MEGASTROKE, 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, ARCADIA Investigators, Jeunemaitre, Xavier, Persu, Alexandre, Kovacic, Jason C, Ganesh, Santhi K, Bouatia-Naji, Nabila, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Département cardiovasculaire, 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, FEIRI investigators, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, MEGASTROKE, 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, ARCADIA Investigators, Jeunemaitre, Xavier, Persu, Alexandre, Kovacic, Jason C, Ganesh, Santhi K, and Bouatia-Naji, Nabila

Abstract

No abstract available

Published
2022

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

Author

UCL - SSS/DDUV/GEHU - Génétique, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Département cardiovasculaire, 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, FEIRI investigators, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, MEGASTROKE, 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, UCL - SSS/DDUV/GEHU - Génétique, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - (SLuc) Département cardiovasculaire, 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, FEIRI investigators, International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, MEGASTROKE, 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, and Bouatia-Naji, Nabila

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.

Published
2021

7. Genetic association studies of fibromuscular dysplasia identify new risk loci and shared genetic basis with more common vascular diseases

Author

Ozan Dikilitas, Marco Pappaccogli, Peter W. de Leeuw, Witold Smigielski, Valentina d'Escamard, Lijiang Ma, Ernst Rietzschel, Kristina L. Hunker, Lu Liu, Michel Azizi, Matthew Zawistowski, Jeffrey W. Olin, Ynte M. Ruigrok, Min-Lee Yang, Stéphanie Debette, Laurence Amar, Xiang Zhou, Sergiy Kyryachenko, Jun Li, Benjamin A. Satterfield, James C. Stanley, Feiri investigators, Miikka Vikkula, Ewa Warchol Celinska, Mengyao Yu, Dawn M. Coleman, Marc De Buyzere, Nabila Bouatia-Naji, Iftikhar J. Kullo, Megastroke, Aleksander Prejbisz, Andrzej Januszewicz, Piotr Dobrowolski, Wojciech Drygas, Takiy-Eddine Berrandou, Jerzy Piwonski, Sebanti Sengupta, Jason C. Kovacic, Mark K Bakker, Santhi K. Ganesh, Xavier Jeunemaitre, Chad M. Brummett, Jean-François Deleuze, Heather L. Gornik, Sebastian Zoellner, Soto Romuald Kiando, Alexandre Persu, Adrien Georges, Aurélien Lorthioir, Natalia Fendrikova-Mahlay, Daniella Kadian-Dodov, and Délia Dupré

Subjects
Pathology, medicine.medical_specialty, Linkage disequilibrium, Vascular smooth muscle, business.industry, Locus (genetics), Fibromuscular dysplasia, Actin cytoskeleton, medicine.disease, Coronary artery disease, Blood pressure, medicine, business, Genetic association
Abstract

Fibromuscular dysplasia (FMD) is an arteriopathy that presents clinically by hypertension and stroke, mostly in early middle-aged women. We report results from the first genome-wide association meta-analysis of FMD including 1962 FMD cases and 7100 controls. We confirmedPHACTR1and identified three new loci (LRP1, ATP2B1, andLIMA1)associated with FMD. Transcriptome-wide association analysis in arteries identified one additional locus (SLC24A3). FMD associated variants were located in arterial-specific enhancers active in vascular smooth muscle cells and fibroblasts. Target genes are broadly involved in mechanisms related to actin cytoskeleton and intracellular calcium homeostasis, central to vascular contraction. Cross-trait linkage disequilibrium analyses identified positive genetic correlations with blood pressure, migraine and intracranial aneurysm, and an inverse correlation with coronary artery disease, independent from the genetics of blood pressure.

Published
2020

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