Evidence map›Paper›PMID 34491620›Full record

ArticleMolecular genetics & genomic medicine2021

Assessing the association of common genetic variants in EPHB4 and RASA1 with phenotype severity in familial cerebral cavernous malformation.

Foram Choksi, Shantel Weinsheimer, Jeffrey Nelson, Ludmila Pawlikowska, Christine K Fox, Atif Zafar, Marc C Mabray, Joseph Zabramski, Amy Akers, Blaine L Hart and 3 more

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

Article in Molecular genetics & genomic medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01764529 (Modifiers of Disease Severity and Progression in Cerebral Cavernous Malformations), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 43% 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.

NCT01764529 completednot on this map

Modifiers of Disease Severity and Progression in Cerebral Cavernous Malformations

Typeobservational_patient_registrySponsorUniversity of California, San FranciscoRan2010 to 2025Enrolled789ConditionsCavernous Angioma, Familial, Cerebral Cavernous Malformations, Cerebral Cavernous Hemangioma
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. iScience · 2026
    Article
  2. Article
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

13 authors at 4 institutions in 1 country.

Foram ChoksiDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0001-7489-0227
Shantel WeinsheimerDepartment of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0001-7486-9110
Jeffrey NelsonDepartment of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California San Francisco, San Francisco, California, USA.
Ludmila PawlikowskaDepartment of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0003-2182-9953
Christine K FoxDepartment of Neurology, University of California San Francisco, San Francisco, California, USA.
Atif ZafarDepartment of Neurology, University of New Mexico, Albquerque, New Mexico, USA.
Marc C MabrayDepartment of Radiology, University of New Mexico, Albquerque, New Mexico, USA.
Joseph ZabramskiDepartment of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona, USA.
Amy AkersAngioma Alliance, Durham, North Carolina, USA.
Blaine L HartDepartment of Radiology, University of New Mexico, Albquerque, New Mexico, USA.
Leslie MorrisonDepartment of Neurology, University of New Mexico, Albquerque, New Mexico, USA.
Charles E McCullochDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.
Helen KimDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0002-1937-354X
University of California, San Francisco · USUniversity of New Mexico · USAngioma Alliance · USBarrow Neurological Institute · US

Funding

The Impact of COVID-19 on People Living with Rare Diseases and Their FamiliesU2CTR002818 · NCATS · CINCINNATI CHILDRENS HOSP MED CTR · PI Michal Kouril · 2019 to 2026
$51.2M
VCRC Administration UnitU54NS065705 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KIM, HELEN · 2009 to 2023
$20.8M
NCATS NIH HHS U2C TR002818NINDS NIH HHS U54 NS065705
6 · The paper itself

Abstract

backgroundTo investigate whether common variants in EPHB4 and RASA1 are associated with cerebral cavernous malformation (CCM) disease severity phenotypes, including intracranial hemorrhage (ICH), total and large lesion counts.

methodsFamilial CCM cases enrolled in the Brain Vascular Malformation Consortium were included (n = 338). Total lesions and large lesions (≥5 mm) were counted on MRI; clinical history of ICH at enrollment was assessed by medical records. Samples were genotyped on the Affymetrix Axiom Genome-Wide LAT1 Human Array. We tested the association of seven common variants (three in EPHB4 and four in RASA1) using multivariable logistic regression for ICH (odds ratio, OR) and multivariable linear regression for total and large lesion counts (proportional increase, PI), adjusting for age, sex, and three principal components. Significance was based on Bonferroni adjustment for multiple comparisons (0.05/7 variants = 0.007).

resultsEPHB4 variants were not significantly associated with CCM severity phenotypes. One RASA1 intronic variant (rs72783711 A>C) was significantly associated with ICH (OR = 1.82, 95% CI = 1.21-2.37, p = 0.004) and nominally associated with large lesion count (PI = 1.17, 95% CI = 1.03-1.32, p = 0.02).

conclusionA common RASA1 variant may be associated with ICH and large lesion count in familial CCM. EPHB4 variants were not associated with any of the three CCM severity phenotypes.

Indexed as

Genetic VariationPhenotypeAdolescentAdultAgedAged, 80 and overAllelesChildChild, PreschoolCross-Sectional StudiesFemaleGenetic Association StudiesGenetic Predisposition to DiseaseHemangioma, Cavernous, Central Nervous SystemHumansInfantEPHB4 protein, humanp120 GTPase Activating ProteinRASA1 protein, humanReceptor, EphB4cerebral cavernous malformationEPHB4RASA1Ras-Erk/Ras-MAPK signalingvascular malformation

Identifiers

PMID34491620
PMCPMC8580075
OpenAlexW3197974555

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.