Evidence map›Paper›PMID 30070759›Full record

ArticleJournal of thrombosis and haemostasis : JTH2018

Genome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity.

M Olsson, T M Stanne, A Pedersen, E Lorentzen, E Kara, A Martinez-Palacian, N P Rønnow Sand, A F Jacobsen, P M Sandset, J J Sidelmann and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

10 citing papers in PubMed, 16 citations in OpenAlex.

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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

14 authors at 5 institutions in 3 countries.

M OlssonDepartment of Pathology and Genetics, Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
T M StanneDepartment of Pathology and Genetics, Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
A PedersenDepartment of Pathology and Genetics, Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
E LorentzenBioinformatics Core Facility, University of Gothenburg, Gothenburg, Sweden.
E KaraInstitute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
A Martinez-PalacianInstitute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
N P Rønnow SandDepartment of Cardiology, Hospital of South West Denmark, Esbjerg and Department of Regional Health Research, Faculty of Health Science, University of Southern Denmark, Esbjerg, Denmark.
A F JacobsenDepartment of Obstetrics, Oslo University Hospital and University of Oslo, Oslo, Norway.
P M SandsetDepartment of Hematology, Oslo University Hospital and University of Oslo, Oslo, Norway.ORCID 0000-0001-5556-8099
J J SidelmannUnit for Thrombosis Research, Department of Regional Health Research, Faculty of Health Science, University of Southern Denmark, Esbjerg, Denmark.
G EngströmDepartment of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
O MelanderDepartment of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
S M KanseInstitute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
C JernDepartment of Pathology and Genetics, Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
University of Gothenburg · SEUniversity of Oslo · NOLund University · SEOslo University Hospital · NOUniversity of Southern Denmark · DK

Funding

The NINDS International Stroke Genetics Consortium StudyU01NS069208 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI HOWARD, GEORGE, KITTNER, STEVEN J · 2010 to 2013
$9.4M
NINDS NIH HHS U01 NS069208
6 · The paper itself

Abstract

Essentials Knowledge of genetic regulators of plasma factor VII activating protease (FSAP) levels is limited. We performed a genome-wide analysis of variants influencing FSAP activity in Scandinavian cohorts. We replicated an association for Marburg-1 and identified an association for a HABP2 stop variant. We identified a novel locus near ADCY2 as a potential additional regulator of FSAP activity. SUMMARY: Background Factor VII-activating protease (FSAP) has roles in both coagulation and fibrinolysis. Recent data indicate its involvement in several other processes, such as vascular remodeling and inflammation. Plasma FSAP activity is highly variable among healthy individuals and, apart from the low-frequency missense variant Marburg-I (rs7080536) in the FSAP-encoding gene HABP2, determinants of this variation are unclear. Objectives To identify novel genetic variants within and outside of the HABP2 locus that influence circulating FSAP activity. Patients/Methods We performed an exploratory genome-wide association study (GWAS) on plasma FSAP activity amongst 3230 Swedish subjects. Directly genotyped rare variants were also analyzed with gene-based tests. Using GWAS, we confirmed the strong association between the Marburg-I variant and FSAP activity. HABP2 was also significant in the gene-based analysis, and remained significant after exclusion of Marburg-I carriers. This was attributable to a rare HABP2 stop variant (rs41292628). Carriers of this stop variant showed a similar reduction in FSAP activity as Marburg-I carriers, and this finding was replicated. A secondary genome-wide significant locus was identified at a 5p15 locus (rs35510613), and this finding requires future replication. This common variant is located upstream of ADCY2, which encodes a protein catalyzing the formation of cAMP. Results and Conclusions This study verified the Marburg-I variant to be a strong regulator of FSAP activity, and identified an HABP2 stop variant with a similar impact on FSAP activity. A novel locus near ADCY2 was identified as a potential additional regulator of FSAP activity.

Indexed as

Genetic LociGenetic VariationAdenylyl CyclasesAdolescentAdultAgedAnimalsCells, CulturedFemaleGenome-Wide Association StudyGenotypeHemostasisHepatocytesHumansMaleMice, Inbred BALB Cadenylyl cyclase 2Adenylyl CyclasesHABP2 protein, humanSerine Endopeptidasesblood coagulation factorsepidemiologygenetic variationhemostasisplasma

Identifiers

PMID30070759
PMCPMC6485504
OpenAlexW2887020518

What OpenQuestion holds

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LicenceCC BY-NC
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 OpenQuestion graph.