Evidence map›Paper›PMID 37128921›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2023

Antithrombin, Protein C, and Protein S: Genome and Transcriptome-Wide Association Studies Identify 7 Novel Loci Regulating Plasma Levels.

Yuekai Ji, Gerard Temprano-Sagrera, Lori A Holle, Allison Bebo, Jennifer A Brody, Ngoc-Quynh Le, Kadri Kangro, Michael R Brown, Angel Martinez-Perez, Colleen M Sitlani and 32 more

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
2.0field-weighted citation impact, top 12% 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.

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

2 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

42 authors at 17 institutions in 8 countries.

Yuekai Ji *Cardiovascular Division, Department of Medicine, University of Minnesota, MN (Y.J.).
Gerard Temprano-Sagrera *Unit of genomics of Complex Disease, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain (G.T.-S., N.-Q.L., A.M.-P., J.C.S., J.M.S., M.S.-L.).ORCID 0000-0001-6136-8915
Lori A HolleDepartment of Pathology and Laboratory Medicine and UNC Blood Research Center, University of North Carolina at Chapel Hill (L.A.H., K.K., D.A.D., A.S.W.).ORCID 0000-0003-1399-2689
Allison BeboHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston (A.B., M.R.B., A.C.M., P.S.d.V.).
Jennifer A BrodyDepartment of Medicine, University of Washington (J.A.B., K.L.W.).ORCID 0000-0001-8509-148X
Ngoc-Quynh LeUnit of genomics of Complex Disease, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain (G.T.-S., N.-Q.L., A.M.-P., J.C.S., J.M.S., M.S.-L.).
Kadri KangroDepartment of Pathology and Laboratory Medicine and UNC Blood Research Center, University of North Carolina at Chapel Hill (L.A.H., K.K., D.A.D., A.S.W.).ORCID 0000-0003-1808-6386
Michael R BrownHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston (A.B., M.R.B., A.C.M., P.S.d.V.).ORCID 0000-0002-5235-9037
Angel Martinez-PerezUnit of genomics of Complex Disease, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain (G.T.-S., N.-Q.L., A.M.-P., J.C.S., J.M.S., M.S.-L.).ORCID 0000-0002-5934-1454
Colleen M SitlaniCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (C.M.S.).ORCID 0000-0001-7656-7482
Pierre SuchonC2VN, INSERM, INRAE, Aix Marseille Univ, France (P.S., P.-E.M.).
Marcus E KleberSYNLAB MVZ für Humangenetik Mannheim, Germany (M.E.K.).
David B EmmertInstitute for Biomedicine (affiliated to the University of Lübeck), Eurac Research, Italy (D.B.E., M.G., C.F., A.A.H.).
Ayse Bilge OzelDepartment of Human Genetics, University of Michigan, C.S. Mott Children's Hospital, Ann Arbor (A.B.O.).
Dre'Von A DobsonDepartment of Pathology and Laboratory Medicine and UNC Blood Research Center, University of North Carolina at Chapel Hill (L.A.H., K.K., D.A.D., A.S.W.).ORCID 0000-0001-5123-5473
Weihong TangDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, MN (W.T., J.S.P.).ORCID 0000-0003-1200-0270
Dolors LlobetUnit of Thrombosis and Hemostasis, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (D.L., J.C.S.).
Russell P TracyDepartment of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington (R.P.T.).ORCID 0000-0002-0080-2420
Jean-François DeleuzeCentre National de Recherche en Génomique Humaine, CEA, France (J.-F.D.).
Graciela E DelgadoVth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Germany (M.E.K., G.E.D., A.P.M., W.M.).
Martin GögeleInstitute for Biomedicine (affiliated to the University of Lübeck), Eurac Research, Italy (D.B.E., M.G., C.F., A.A.H.).ORCID 0000-0003-4785-4348
Kerri L WigginsDepartment of Medicine, University of Washington (J.A.B., K.L.W.).ORCID 0000-0003-2749-1279
Juan Carlos SoutoUnit of genomics of Complex Disease, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain (G.T.-S., N.-Q.L., A.M.-P., J.C.S., J.M.S., M.S.-L.).ORCID 0000-0003-2092-5142
James S PankowDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, MN (W.T., J.S.P.).ORCID 0000-0001-7076-483X
Kent D TaylorThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, CA (K.D.T.).ORCID 0000-0002-2756-4370
David-Alexandre TrégouëtLaboratory of Excellence on Medical Genomics (GenMed), France (J.-F.D., D.-A.T.).ORCID 0000-0001-9084-7800
Angela P MoisslVth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Germany (M.E.K., G.E.D., A.P.M., W.M.).ORCID 0000-0003-0302-2136
Christian FuchsbergerInstitute for Biomedicine (affiliated to the University of Lübeck), Eurac Research, Italy (D.B.E., M.G., C.F., A.A.H.).
Frits R RosendaalDepartment of Clinical Epidemiology, Leiden University Medical Center, the Netherlands (F.R.R.).ORCID 0000-0003-2558-7496
Alanna C MorrisonHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston (A.B., M.R.B., A.C.M., P.S.d.V.).ORCID 0000-0001-6381-4296
Jose Manuel SoriaUnit of genomics of Complex Disease, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain (G.T.-S., N.-Q.L., A.M.-P., J.C.S., J.M.S., M.S.-L.).ORCID 0000-0002-6226-4293
Mary CushmanLarner College of Medicine, University of Vermont, Burlington (M.C.).ORCID 0000-0002-7871-6143
Pierre-Emmanuel MorangeC2VN, INSERM, INRAE, Aix Marseille Univ, France (P.S., P.-E.M.).
Winfried MärzVth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Germany (M.E.K., G.E.D., A.P.M., W.M.).
Andrew A HicksInstitute for Biomedicine (affiliated to the University of Lübeck), Eurac Research, Italy (D.B.E., M.G., C.F., A.A.H.).ORCID 0000-0001-6320-0411
Karl C DeschDepartment of Pediatrics, University of Michigan, C.S. Mott Children's Hospital, Ann Arbor (K.C.D.).
Andrew D JohnsonNational Heart Lung and Blood Institute, Division of Intramural Research, Population Sciences Branch, The Framingham Heart Study, MA (A.D.J.).ORCID 0000-0001-6369-5178
Paul S de VriesHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston (A.B., M.R.B., A.C.M., P.S.d.V.).ORCID 0000-0003-0964-0111
CHARGE Consortium Hemostasis Working Group, INVENT Consortium
Alisa S WolbergDepartment of Pathology and Laboratory Medicine and UNC Blood Research Center, University of North Carolina at Chapel Hill (L.A.H., K.K., D.A.D., A.S.W.).ORCID 0000-0002-2845-2303
Nicholas L Smith *Department of Epidemiology, University of Washington, Seattle (N.L.S.).ORCID 0000-0003-3483-353X
Maria Sabater-Lleal *Unit of genomics of Complex Disease, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain (G.T.-S., N.-Q.L., A.M.-P., J.C.S., J.M.S., M.S.-L.).ORCID 0000-0002-0128-379X
Biomedical Research Institute · USInstitute for Biomedicine · ITThe University of Texas Health Science Center at Houston · USUniversity of North Carolina at Chapel Hill · USUniversity of Washington · USInserm · FRUniversity of Minnesota · USC. S. Mott Children's Hospital · USHeidelberg University · DEHospital de Sant Pau · ESSynlab Czech (Czechia) · CZUniversity of Vermont · USCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRFramingham Heart Study · USKarolinska Institutet · SELeiden University Medical Center · NLUCLA Medical Center · US

Funding

Cardiovascular Genomics and Bioinformatics projectsZIAHL006170 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI JOHNSON, ANDREW · 2013 to 2025
$25.3M
Epidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
Analysis of Whole Genome Sequence and Hemostasis PhenotypesR01HL139553 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI PAUL STEFAN DE VRIES, Alanna C Morrison · 2018 to 2026
$5.0M
Using genomics and functional biology to understand fibrinogen and its effect on thrombotic and atherosclerotic outcomesR01HL141291 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Alanna C Morrison, Alisa S. Wolberg · 2019 to 2026
$4.6M
Fibrinogen and Factor XIII in Venous ThrombosisR01HL126974 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Alisa S. Wolberg · 2016 to 2026
$4.4M
Population genomic variation, functional biology, and the risk of venous thrombosisR01HL134894 · NHLBI · UNIVERSITY OF WASHINGTON · PI LOWENSTEIN, CHARLES J, SMITH, NICHOLAS L · 2017 to 2020
$2.9M
The Molecular Genetics of Venous Thromboembolic DiseaseR01HL141399 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DESCH, KARL C · 2018 to 2022
$1.9M
NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL126974NHLBI NIH HHS R01 HL134894NHLBI NIH HHS R01 HL139553NHLBI NIH HHS R01 HL141291NHLBI NIH HHS R01 HL141399
6 · The paper itself

Abstract

backgroundAntithrombin, PC (protein C), and PS (protein S) are circulating natural anticoagulant proteins that regulate hemostasis and of which partial deficiencies are causes of venous thromboembolism. Previous genetic association studies involving antithrombin, PC, and PS were limited by modest sample sizes or by being restricted to candidate genes. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, we meta-analyzed across ancestries the results from 10 genome-wide association studies of plasma levels of antithrombin, PC, PS free, and PS total.

methodsStudy participants were of European and African ancestries, and genotype data were imputed to TOPMed, a dense multiancestry reference panel. Each of the 10 studies conducted a genome-wide association studies for each phenotype and summary results were meta-analyzed, stratified by ancestry. Analysis of antithrombin included 25 243 European ancestry and 2688 African ancestry participants, PC analysis included 16 597 European ancestry and 2688 African ancestry participants, PSF and PST analysis included 4113 and 6409 European ancestry participants. We also conducted transcriptome-wide association analyses and multiphenotype analysis to discover additional associations. Novel genome-wide association studies and transcriptome-wide association analyses findings were validated by in vitro functional experiments. Mendelian randomization was performed to assess the causal relationship between these proteins and cardiovascular outcomes.

resultsGenome-wide association studies meta-analyses identified 4 newly associated loci: 3 with antithrombin levels (

conclusionsThe use of larger sample sizes, diverse populations, and a denser imputation reference panel allowed the detection of 7 novel genomic loci associated with plasma antithrombin, PC, and PS levels.

Indexed as

Protein CProtein SAnticoagulantsAntithrombin IIIAntithrombinsGenome-Wide Association StudyPolymorphism, Single NucleotideTranscriptomeAnticoagulantsAntithrombin IIIAntithrombinsProtein CProtein Santicoagulantantithrombingenome-wide association studygenotypehemostasisprotein Cprotein S

Identifiers

PMID37128921
PMCPMC10330350
OpenAlexW4367182025

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

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 Socratic graph.