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

Journal Article (Journal 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.

Full Text

Duke Authors

Cited Authors

  • Georges, A; Yang, M-L; Berrandou, T-E; Bakker, MK; Dikilitas, O; Kiando, SR; Ma, L; Satterfield, BA; Sengupta, S; Yu, M; Deleuze, J-F; Dupré, D; Hunker, KL; Kyryachenko, S; Liu, L; Sayoud-Sadeg, I; Amar, L; Brummett, CM; Coleman, DM; d'Escamard, V; de Leeuw, P; Fendrikova-Mahlay, N; Kadian-Dodov, D; Li, JZ; Lorthioir, A; Pappaccogli, M; Prejbisz, A; Smigielski, W; Stanley, JC; Zawistowski, M; Zhou, X; Zöllner, S; FEIRI investigators, ; International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group, ; MEGASTROKE, ; Amouyel, P; De Buyzere, ML; Debette, S; Dobrowolski, P; Drygas, W; Gornik, HL; Olin, JW; Piwonski, J; Rietzschel, ER; Ruigrok, YM; Vikkula, M; Warchol Celinska, E; Januszewicz, A; Kullo, IJ; Azizi, M; ARCADIA Investigators, ; Jeunemaitre, X; Persu, A; Kovacic, JC; Ganesh, SK; Bouatia-Naji, N

Published Date

  • October 15, 2021

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 6031 -

PubMed ID

  • 34654805

Pubmed Central ID

  • PMC8521585

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-021-26174-2


  • eng

Conference Location

  • England