Evidence map›Paper›PMID 41026970›Full record

ArticleBlood advances2026

Population-scale analysis reveals inherited C1-inhibitor deficiency is a polyphenotypic thrombotic disorder.

Alfonso Rodriguez Espada, Amelia K Haj, Sean J Jurgens, Harish Eswaran, Linda Sundler Björkman, Justine Ryu, Sharjeel Chaudhry, Satoshi Koyama, Xin Wang, Seung Hoan Choi and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Therapeutic Potential of C1-Inhibitor in Vascular Diseases and Beyond.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Alfonso Rodriguez EspadaCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.ORCID 0009-0007-6743-5390
Amelia K HajCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.ORCID 0000-0002-1453-341X
Sean J JurgensCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.ORCID 0000-0002-1605-9782
Harish EswaranDivision of Hematology, Department of Medicine, UNC Blood Research Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC.
Linda Sundler BjörkmanDivision of Hematology, Department of Medicine, UNC Blood Research Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC.ORCID 0000-0003-4146-9983
Justine RyuCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.
Sharjeel ChaudhryCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.
Satoshi KoyamaCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.ORCID 0000-0002-9286-0360
Xin WangCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.
Seung Hoan ChoiCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.ORCID 0000-0002-2797-3190
Simone Sanna-CherchiDivision of Nephrology, Columbia University Irving Medical Center, New York, NY.ORCID 0000-0002-6185-948X
Aleena BanerjiHarvard Medical School, Boston, MA.
Joel T RämöCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.ORCID 0000-0002-6429-5149
Patrick T EllinorCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.ORCID 0000-0002-2067-0533
Steven P GroverDivision of Hemostasis and Thrombosis, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA.ORCID 0000-0001-8709-8394
Pavan K BendapudiCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA.ORCID 0000-0002-0754-7688

Funding

Research Training in Hematology at UNC Chapel HillT32HL007149 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Nigel S. Key · 1985 to 2026
$8.6M
NHLBI NIH HHS T32 HL007149
6 · The paper itself

Abstract

abstractDeficiency in C1 inhibitor (C1INH/SERPING1) is canonically associated with hereditary angioedema (HAE-C1INH) but not thrombosis. To determine the thrombosis risk conferred by the loss of C1INH in the general population, we studied genetically-defined C1INH deficiency across 635 823 participants. Functionally deleterious germ line coding variation in the SERPING1 gene was rare (∼1:10 000), indicating strong genetic constraint. SERPING1 variant carriers had significantly lower plasma C1INH levels than noncarriers, as determined by Olink proteomics (P = .005) and confirmed by enzyme-linked immunosorbent assay in an independent cohort (P< .001). After adjustment for sex and ancestry, SERPING1 haploinsufficiency was associated with a significantly increased risk of venous thromboembolism (hazard ratio [HR], 4.64; 95% confidence interval [CI], 2.08-10.34; P = .0002), noncardioembolic ischemic stroke (HR, 3.29; 95% CI, 1.06-10.19; P = .039), and peripheral artery disease (HR, 3.10; 95% CI, 1.29-7.45; P = .011), with a trend toward association with myocardial infarction (HR, 2.77; 95% CI, 0.89-8.61; P = .077). Effect size estimates for all 4 thrombosis phenotypes increased when analysis was restricted to only the most functionally deleterious variants. These findings highlight the potential of population-scale data sets to address fundamental questions related to thrombosis risk.

Indexed as

Complement C1 Inhibitor ProteinThrombosisAdultAgedFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedPhenotypeComplement C1 Inhibitor ProteinSERPING1 protein, human

Identifiers

PMID41026970
PMCPMC12905601

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.