Genetic association studies of fibromuscular dysplasia identify new risk loci and shared genetic basis with more common vascular diseases
Genetic association studies of fibromuscular dysplasia identify new risk loci and shared genetic basis with more common vascular diseases
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 confirmed PHACTR1 and identified three new loci (LRP1, ATP2B1, and LIMA1) 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.
Rietzschel Ernst R.、Berrandou Takiy-Eddine、Bakker Mark、Dikilitas Ozan、Brummett Chad M.、Georges Adrien、Stanley James C.、Zawistowski Matthew、FEIRI investigators、Dobrowolski Piotr、Drygas Wojciech、Olin Jeffrey W.、Satterfield Benjamin A.、Sengupta Sebanti、Kyryachenko Sergiy、de Leeuw Peter、Kullo Iftikhar J.、Ganesh Santhi K.、Jeunemaitre Xavier、Debette St¨|phanie、Vikkula Miikka、Kiando Soto Romuald、Kadian-Dodov Daniella、De Buyzere Marc L.、Hunker Kristina L.、Piwonski Jerzy、Yang Min-Lee、Yu Mengyao、Kovacic Jason C.、Azizi Michel、Pappaccogli Marco、Dupr¨| Delia、International stroke genetics consortium (ISGC) intracranial aneurysm working group、Bouatia-Naji Nabila、Coleman Dawn M.、Ruigrok Ynte、Smigielski Witold、Lorthioir Aur¨|lien、Zhou Xiang、Li Jun Z.、Liu Lu、Fendrikova-Mahlay Natalia、Persu Alexandre、d?ˉEscamard Valentina、Prejbisz Aleksander、Deleuze Jean-Fran?ois、Amar Laurence、Celinska Ewa Warchol、Zoellner Sebastian、Januszewicz Andrzej、Ma Lijiang、Megastroke、Gornik Heather L.
Department of Cardiovascular Diseases, Ghent University and Ghent University HospitalUniversit¨| de Paris, INSERM, Paris Cardiovascular Research CenterDepartment of Neurology and Neurosurgery, University Medical Center Utrecht Brain Center, Utrecht UniversityDepartment of Cardiovascular MedicineDepartment of Anesthesiology, Michigan Medicine, University of MichiganUniversit¨| de Paris, INSERM, Paris Cardiovascular Research CenterVascular Surgery Section, Department of Surgery, Michigan Medicine, University of MichiganDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthA full list of authors and their affiliations is provided in the supplementary material.Department of Hypertension, National Institute of CardiologyDepartment of Epidemiology, Cardiovascular Disease Prevention, and Health Promotion, National Institute of CardiologyZena and Michael A. Wiener Cardiovascular Institute and Marie-Jos¨|e and Henry R. Kravis Center for Cardiovascular Health Icahn School of Medicine at Mount SinaiDepartment of Cardiovascular MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical SchoolUniversit¨| de Paris, INSERM, Paris Cardiovascular Research CenterDepartment of Internal Medicine, Division of General Internal Medicine, Section Vascular Medicine, Maastricht University Medical Centre, Maastricht University||CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht UniversityDepartment of Cardiovascular MedicineDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School||Department of Human Genetics, University of Michigan Medical SchoolUniversit¨| de Paris, INSERM, Paris Cardiovascular Research Center||Department of Genetics, Assistance-Publiques-H?pitaux de Paris, H?pital Europ¨|en Georges PompidouDepartment of Neurology, Bordeaux University HospitalHuman Molecular Genetics, de Duve Institute, Universit¨| Catholique de LouvainUniversit¨| de Paris, INSERM, Paris Cardiovascular Research CenterZena and Michael A. Wiener Cardiovascular Institute and Marie-Jos¨|e and Henry R. Kravis Center for Cardiovascular Health Icahn School of Medicine at Mount SinaiDepartment of Cardiovascular Diseases, Ghent University and Ghent University HospitalDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School||Department of Human Genetics, University of Michigan Medical SchoolDepartment of Epidemiology, Cardiovascular Disease Prevention, and Health Promotion, National Institute of CardiologyDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School||Department of Human Genetics, University of Michigan Medical SchoolUniversit¨| de Paris, INSERM, Paris Cardiovascular Research CenterIcahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai||Victor Chang Cardiac Research Institute||University of New South WalesHypertension Unit, Assistance Publique-H?pitaux de Paris, H?pital Europ¨|en Georges Pompidou||Universit¨| de Paris, Inserm, Centre d?ˉInvestigation Clinique 1418Division of Cardiology, Cliniques Universitaires Saint-Luc, Universit¨| Catholique de Louvain||Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, University of TurinUniversit¨| de Paris, INSERM, Paris Cardiovascular Research CenterA full list of authors and their affiliations is provided in the supplementary material.Universit¨| de Paris, INSERM, Paris Cardiovascular Research CenterVascular Surgery Section, Department of Surgery, Michigan Medicine, University of MichiganDepartment of Neurology and Neurosurgery, University Medical Center Utrecht Brain Center, Utrecht UniversityDepartment of Demography, University of LodzUniversit¨| de Paris, INSERM, Paris Cardiovascular Research Center||Hypertension Unit, Assistance Publique-H?pitaux de Paris, H?pital Europ¨|en Georges PompidouDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthDepartment of Human Genetics, University of Michigan Medical SchoolUniversit¨| de Paris, INSERM, Paris Cardiovascular Research CenterHeart and Vascular Institute, Cleveland Clinic, ClevelandDivision of Cardiology, Cliniques Universitaires Saint-Luc, Universit¨| Catholique de Louvain||Pole of Cardiovascular Research, Institut de Recherche Exp¨|rimentale et Clinique, Universit¨| Catholique de LouvainCardiovascular Institute, Icahn School of Medicine at Mount SinaiDepartment of Hypertension, National Institute of CardiologyCentre National de Recherche en G¨|nomique Humaine, Institut de G¨|nomique, CEA and Fondation Jean Dausset-CEPHUniversit¨| de Paris, INSERM, Paris Cardiovascular Research Center||Hypertension Unit, Assistance Publique-H?pitaux de Paris, H?pital Europ¨|en Georges PompidouDepartment of Hypertension, National Institute of CardiologyDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthDepartment of Hypertension, National Institute of CardiologyIcahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount SinaiA full list of authors and their affiliations is provided in the supplementary material.||Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE - Labex DISTALZ - Risk factors and molecular determinants of aging-related diseaseHeart and Vascular Institute, Cleveland Clinic, Cleveland
基础医学遗传学生理学
Rietzschel Ernst R.,Berrandou Takiy-Eddine,Bakker Mark,Dikilitas Ozan,Brummett Chad M.,Georges Adrien,Stanley James C.,Zawistowski Matthew,FEIRI investigators,Dobrowolski Piotr,Drygas Wojciech,Olin Jeffrey W.,Satterfield Benjamin A.,Sengupta Sebanti,Kyryachenko Sergiy,de Leeuw Peter,Kullo Iftikhar J.,Ganesh Santhi K.,Jeunemaitre Xavier,Debette St¨|phanie,Vikkula Miikka,Kiando Soto Romuald,Kadian-Dodov Daniella,De Buyzere Marc L.,Hunker Kristina L.,Piwonski Jerzy,Yang Min-Lee,Yu Mengyao,Kovacic Jason C.,Azizi Michel,Pappaccogli Marco,Dupr¨| Delia,International stroke genetics consortium (ISGC) intracranial aneurysm working group,Bouatia-Naji Nabila,Coleman Dawn M.,Ruigrok Ynte,Smigielski Witold,Lorthioir Aur¨|lien,Zhou Xiang,Li Jun Z.,Liu Lu,Fendrikova-Mahlay Natalia,Persu Alexandre,d?ˉEscamard Valentina,Prejbisz Aleksander,Deleuze Jean-Fran?ois,Amar Laurence,Celinska Ewa Warchol,Zoellner Sebastian,Januszewicz Andrzej,Ma Lijiang,Megastroke,Gornik Heather L..Genetic association studies of fibromuscular dysplasia identify new risk loci and shared genetic basis with more common vascular diseases[EB/OL].(2025-03-28)[2025-08-02].https://www.medrxiv.org/content/10.1101/2020.09.16.20195701.点此复制
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