Evidence map›Paper›PMID 27792790›Full record

ArticlePLoS genetics2016

PHACTR1 Is a Genetic Susceptibility Locus for Fibromuscular Dysplasia Supporting Its Complex Genetic Pattern of Inheritance.

Soto Romuald Kiando, Nathan R Tucker, Luis-Jaime Castro-Vega, Alexander Katz, Valentina D'Escamard, Cyrielle Tréard, Daniel Fraher, Juliette Albuisson, Daniella Kadian-Dodov, Zi Ye and 23 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01967511 (Defining the Basis of Fibromuscular Dysplasia), which is not on this map. Cited by 81 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 3 pooled it
17.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01967511 recruitingnot on this map

Defining the Basis of Fibromuscular Dysplasia: The Define-FMD Study

TypeobservationalSponsorIcahn School of Medicine at Mount SinaiRan2013 to 2030Enrolled600ConditionsFibromuscular Dysplasia, Spontaneous Coronary Artery Dissection, Cervical Artery Dissection
3 · Its place in the literature

Who cites it

81 citing papers in PubMed, 3 syntheses or guidelines pooled it, 190 citations in OpenAlex.

  1. Characteristics of Asian patients with Fibromuscular Dysplasia: a systematic review and meta-analysis.Hypertension research : official journal of the Japanese Society of Hypertension · 2025
    Pooled it
  2. Pooled it
  3. Guideline
  4. Review
  5. Review
  6. Fibromuscular dysplasia presenting with bronchial artery involvement.Journal of vascular surgery cases and innovative techniques · 2026
    Article
  7. Article
  8. Cerebrovascular fibromuscular dysplasia.Therapeutic advances in neurological disorders · 2026
    Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Association ofJournal of cardiovascular development and disease · 2024
    Article

21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

33 authors at 9 institutions in 3 countries.

Soto Romuald KiandoINSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE.ORCID http://orcid.org/0000-0001-9492-5730
Nathan R TuckerCardiovascular research Center, Massachusetts General Hospital, Charlestown, MA 02114, USA, Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA 02142.
Luis-Jaime Castro-VegaINSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE.
Alexander KatzDepartment of Internal Medicine and Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Valentina D'EscamardThe Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine, Marie-Josée and Henry R. Kravis Cardiovascular Health Center at Mount Sinai, One Gustave L. Levy Place, Box 1030 New York, NY 10029, New York, NY, USA.
Cyrielle TréardINSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE.
Daniel FraherCardiovascular research Center, Massachusetts General Hospital, Charlestown, MA 02114, USA, Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA 02142.
Juliette AlbuissonINSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE.
Daniella Kadian-DodovThe Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine, Marie-Josée and Henry R. Kravis Cardiovascular Health Center at Mount Sinai, One Gustave L. Levy Place, Box 1030 New York, NY 10029, New York, NY, USA.
Zi YeDepartment of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
Erin AustinDepartment of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
Min-Lee YangDepartment of Internal Medicine and Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Kristina HunkerDepartment of Internal Medicine and Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Cristina BarlassinaDept. of Health Sciences, Genomic and Bioinformatics Unit, Viale Ortles 22/4, Milano, Chair and Graduate School of Nephrology, University of Milano, Division of Nephrology, San Paolo Hospital, Milano, 20142,ITALY.ORCID http://orcid.org/0000-0001-7407-2697
Daniele CusiInstitute of Biomedical Technologies, Italian National Centre of Research, Via F.lli Cervi 93, 20090 Segrate - Milano.
Pilar GalanNutritional Epidemiology Research Group, Sorbonne-Paris-Cité, UMR University of Paris 13/Inserm U-557/INRA U-1125/CNAM, Bobigny, France F-93017, Bobigny, FRANCE.
Jean-Philippe EmpanaINSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE.
Xavier JouvenINSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE.
Anne-Paule Gimenez-RoqueploINSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE.
Patrick BrunevalINSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE.
Esther Soo Hyun KimDepartment of Cardiovascular Medicine, Cleveland Clinic Heart and Vascular Institute, Cleveland, OH 44195, USA.
Jeffrey W OlinThe Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine, Marie-Josée and Henry R. Kravis Cardiovascular Health Center at Mount Sinai, One Gustave L. Levy Place, Box 1030 New York, NY 10029, New York, NY, USA.
Heather L GornikDepartment of Cardiovascular Medicine, Cleveland Clinic Heart and Vascular Institute, Cleveland, OH 44195, USA.ORCID http://orcid.org/0000-0002-5849-4010
Michel AziziParis-Descartes University, Sorbonne Paris Cité, Paris 75006, FRANCE.
Pierre-François PlouinINSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE.
Patrick T EllinorCardiovascular research Center, Massachusetts General Hospital, Charlestown, MA 02114, USA, Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA 02142.
Iftikhar J KulloDepartment of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
David J MilanCardiovascular research Center, Massachusetts General Hospital, Charlestown, MA 02114, USA, Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA 02142.
Santhi K GaneshDepartment of Internal Medicine and Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Pierre BoutouyrieINSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE.
Jason C KovacicThe Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine, Marie-Josée and Henry R. Kravis Cardiovascular Health Center at Mount Sinai, One Gustave L. Levy Place, Box 1030 New York, NY 10029, New York, NY, USA.ORCID http://orcid.org/0000-0003-4555-769X
Xavier JeunemaitreINSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE.ORCID http://orcid.org/0000-0001-5925-381X
Nabila Bouatia-NajiINSERM, UMR970 Paris Cardiovascular Research Center (PARCC), Paris F-75015, FRANCE.
Délégation Paris 5 · FRBroad Institute · USCardiovascular Institute of the South · USUniversity of Michigan · USMayo Clinic · USCleveland Clinic · USConservatoire National des Arts et Métiers · FRInstitute of Biomedical Technologies · ITUniversity of Milan · IT

Funding

CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024989 · NCRR · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B · 2007 to 2011
$53.7M
Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6M
MULTIDISCIPLINARY RESEARCH TRAINING IN CARDIOLOGYT32HL007208 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Patrick Thomas Ellinor, David E Sosnovik · 1985 to 2026
$16.1M
TRAINING PROGRAM IN MOLECULAR AND CELLULAR CARDIOLOGYT32HL007824 · NHLBI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI GELB, BRUCE D · 1995 to 2022
$8.6M
Training Program in Cardiovascular ResearchT32HL007374 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MITTLEMAN, MURRAY A · 1985 to 2019
$7.9M
AFGen Consortium: Atrial Fibrillation Genomics to Functional AnalysesR01HL128914 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2015 to 2018
$3.1M
Genetics and Mechanisms of Mitral Valve ProlapseR01HL127692 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI MILAN, DAVID J, SLAUGENHAUPT, SUSAN A · 2015 to 2018
$3.0M
Mentoring in Arrhythmia ResearchK24HL105780 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2011 to 2020
$1.2M
NCATS NIH HHS UL1 TR000439NCRR NIH HHS UL1 RR024989NHLBI NIH HHS K24 HL105780NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL127692NHLBI NIH HHS R01 HL128914NHLBI NIH HHS T32 HL007208NHLBI NIH HHS T32 HL007374NHLBI NIH HHS T32 HL007824
6 · The paper itself

Abstract

Fibromuscular dysplasia (FMD) is a nonatherosclerotic vascular disease leading to stenosis, dissection and aneurysm affecting mainly the renal and cerebrovascular arteries. FMD is often an underdiagnosed cause of hypertension and stroke, has higher prevalence in females (~80%) but its pathophysiology is unclear. We analyzed ~26K common variants (MAF>0.05) generated by exome-chip arrays in 249 FMD patients and 689 controls. We replicated 13 loci (P<10-4) in 402 cases and 2,537 controls and confirmed an association between FMD and a variant in the phosphatase and actin regulator 1 gene (PHACTR1). Three additional case control cohorts including 512 cases and 669 replicated this result and overall reached the genomic level of significance (OR = 1.39, P = 7.4×10-10, 1,154 cases and 3,895 controls). The top variant, rs9349379, is intronic to PHACTR1, a risk locus for coronary artery disease, migraine, and cervical artery dissection. The analyses of geometrical parameters of carotids from ~2,500 healthy volunteers indicate higher intima media thickness (P = 1.97×10-4) and wall to lumen ratio (P = 0.002) in rs9349379-A carriers, suggesting indices of carotid hypertrophy previously described in carotids of FMD patients. Immunohistochemistry detected PHACTR1 in endothelium and smooth muscle cells of FMD and normal human carotids. The expression of PHACTR1 by genotypes in primary human fibroblasts showed higher expression in rs9349379-A carriers (N = 86, P = 0.003). Phactr1 knockdown in zebrafish resulted in dilated vessels indicating subtle impaired vascular development. We report the first susceptibility locus for FMD and provide evidence for a complex genetic pattern of inheritance and indices of shared pathophysiology between FMD and other cardiovascular and neurovascular diseases.

Indexed as

Genetic Association StudiesGenetic Predisposition to DiseaseAnimalsArteriesCarotid ArteriesCarotid Intima-Media ThicknessDisease Models, AnimalExomeFemaleFibromuscular DysplasiaGene Expression RegulationGenotypeHumansHypertensionMaleMicrofilament ProteinsMicrofilament ProteinsPHACTR1 protein, human

Identifiers

PMID27792790
PMCPMC5085032
OpenAlexW2540838358

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.