Evidence map›Paper›PMID 35978133›Full record

SynthesisCommunications biology2022

Inframe insertion and splice site variants in MFGE8 associate with protection against coronary atherosclerosis.

Sanni E Ruotsalainen, Ida Surakka, Nina Mars, Juha Karjalainen, Mitja Kurki, Masahiro Kanai, Kristi Krebs, Sarah Graham, Pashupati P Mishra, Binisha H Mishra and 13 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

14 citing papers in PubMed, 18 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

23 authors at 20 institutions in 8 countries.

Sanni E RuotsalainenInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-1631-4069
Ida SurakkaDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Nina MarsInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
Juha KarjalainenThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Mitja KurkiThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Masahiro KanaiThe Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-5165-4408
Kristi KrebsEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.ORCID 0000-0003-0494-2751
Sarah GrahamDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Pashupati P MishraDepartment of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Binisha H MishraDepartment of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Juha SinisaloHeart and Lung Center, Helsinki University Hospital and Helsinki University, Helsinki, Finland.
Priit PaltaInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.ORCID 0000-0001-9320-7008
Terho LehtimäkiDepartment of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Olli RaitakariResearch Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Estonian Biobank Research Team
Lili MilaniEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Biobank Japan Project
Yukinori OkadaDepartment of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.ORCID 0000-0002-0311-8472
FinnGen
Aarno PalotieInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-2527-5874
Elisabeth WidenInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
Mark J DalyInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
Samuli RipattiInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland. samuli.ripatti@helsinki.fi.ORCID 0000-0002-0504-1202
University of Helsinki · FIHospital District of Helsinki and Uusimaa · FIBroad Institute · USFinnish Institute for Health and Welfare · FIGlaxoSmithKline (United Kingdom) · GBNorthern Ostrobothnia Hospital District · FIVarsinais-Suomen Sairaanhoitopiiri · FIAbbVie (United States) · USBiogen (United States) · USPfizer (United States) · USPirkanmaa Hospital District · FISanofi (France) · FRTampere University · FIBristol-Myers Squibb (United States) · USUniversity of Turku · FIMerck & Co., Inc., Rahway, NJ, USA (United States) · USNovartis (Switzerland) · CHAstraZeneca (United Kingdom) · GBUniversity of Tartu · EEBorealis (Finland) · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cardiovascular diseases are the leading cause of premature death and disability worldwide, with both genetic and environmental determinants. While genome-wide association studies have identified multiple genetic loci associated with cardiovascular diseases, exact genes driving these associations remain mostly uncovered. Due to Finland's population history, many deleterious and high-impact variants are enriched in the Finnish population giving a possibility to find genetic associations for protein-truncating variants that likely tie the association to a gene and that would not be detected elsewhere. In a large Finnish biobank study FinnGen, we identified an association between an inframe insertion rs534125149 in MFGE8 (encoding lactadherin) and protection against coronary atherosclerosis. This variant is highly enriched in Finland, and the protective association was replicated in meta-analysis of BioBank Japan and Estonian biobank. Additionally, we identified a protective association between splice acceptor variant rs201988637 in MFGE8 and coronary atherosclerosis, independent of the rs534125149, with no significant risk-increasing associations. This variant was also associated with lower pulse pressure, pointing towards a function of MFGE8 in arterial aging also in humans in addition to previous evidence in mice. In conclusion, our results suggest that inhibiting the production of lactadherin could lower the risk for coronary heart disease substantially.

Indexed as

Cardiovascular DiseasesCoronary Artery DiseaseAnimalsAntigens, SurfaceGenetic LociGenome-Wide Association StudyHumansMiceMilk ProteinsPolymorphism, Single NucleotideAntigens, SurfaceMFGE8 protein, humanMfge8 protein, mouseMilk Proteins

Identifiers

PMID35978133
PMCPMC9385630
OpenAlexW4292323902

What Socratic holds

Textmetadata
LicenceCC BY
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.