TY - JOUR
T1 - Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases
AU - FEIRI investigators
AU - International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group
AU - MEGASTROKE
AU - Georges, Adrien
AU - Yang, Min Lee
AU - Berrandou, Takiy Eddine
AU - Bakker, Mark K.
AU - Dikilitas, Ozan
AU - Kiando, Soto Romuald
AU - Ma, Lijiang
AU - Satterfield, Benjamin A.
AU - Sengupta, Sebanti
AU - Yu, Mengyao
AU - Deleuze, Jean François
AU - Dupré, Delia
AU - Hunker, Kristina L.
AU - Kyryachenko, Sergiy
AU - Liu, Lu
AU - Sayoud-Sadeg, Ines
AU - Amar, Laurence
AU - Brummett, Chad M.
AU - Coleman, Dawn M.
AU - d’Escamard, Valentina
AU - de Leeuw, Peter
AU - Fendrikova-Mahlay, Natalia
AU - Kadian-Dodov, Daniella
AU - Li, Jun Z.
AU - Lorthioir, Aurélien
AU - Pappaccogli, Marco
AU - Prejbisz, Aleksander
AU - Smigielski, Witold
AU - Stanley, James C.
AU - Zawistowski, Matthew
AU - Zhou, Xiang
AU - Zöllner, Sebastian
AU - de Leeuw, Peter
AU - Amouyel, Philippe
AU - De Buyzere, Marc L.
AU - Debette, Stéphanie
AU - Dobrowolski, Piotr
AU - Drygas, Wojciech
AU - Gornik, Heather L.
AU - Olin, Jeffrey W.
AU - Piwonski, Jerzy
AU - Rietzschel, Ernst R.
AU - Ruigrok, Ynte M.
AU - Vikkula, Miikka
AU - Warchol Celinska, Ewa
AU - Januszewicz, Andrzej
AU - Kullo, Iftikhar J.
AU - Azizi, Michel
AU - Jeunemaitre, Xavier
AU - Persu, Alexandre
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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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U2 - 10.1038/s41467-021-26174-2
DO - 10.1038/s41467-021-26174-2
M3 - Article
C2 - 34654805
AN - SCOPUS:85119089555
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 6031
ER -