Evidence map›Paper›PMID 29040868›Full record

SynthesisAtherosclerosis2017

Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation.

Rona J Strawbridge, Angela Silveira, Marcel den Hoed, Stefan Gustafsson, Jian'an Luan, Denis Rybin, Josée Dupuis, Ruifang Li-Gao, Maryam Kavousi, Abbas Dehghan and 39 more

Open access · bronzeAbstract readMeta-AnalysisMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Atherosclerosis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.2field-weighted citation impact, top 32% 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

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 3 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Postloading insulinemia is independently associated with arterial stiffness in young Japanese persons.Hypertension research : official journal of the Japanese Society of Hypertension · 2021
    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

49 authors at 19 institutions in 7 countries.

Rona J StrawbridgeCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Mental Health and Wellbeing, Institute of Mental Health and Wellbeing, University of Glasgow, Glasgow, UK. Electronic address: Rona.Strawbridge@ki.se.
Angela SilveiraCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Marcel den HoedDepartment of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Stefan GustafssonDepartment of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Jian'an LuanMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Denis RybinBoston University Data Coordinating Center, Boston, MA, USA.
Josée DupuisDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
Ruifang Li-GaoDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Maryam KavousiDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
Abbas DehghanDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, The Netherlands; MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, UK.
Kadri HaljasDepartment of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Jari LahtiDepartment of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Folkhälsan Research Centre, Helsinki, Finland.
Jesper R GådinCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Alexandra BäcklundCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Ulf de FaireDivision of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
Karl GertowCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Phillipe GiralAssistance Publique-Hôpitaux de Paris, Service Endocrinologie-Métabolisme, Groupe Hospitalier Pitié-Salpétrière, Unités de Prévention Cardiovasculaire, Paris, France.
Anuj GoelWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Steve E HumphriesCentre for Cardiovascular Genetics, Institute Cardiovascular Science, University College London, UK.
Sudhir KurlInstitute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, Kuopio, Finland.
Claudia LangenbergMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
Lars L LannfeltDepartment of Public Health and Caring Sciences, Geriatrics, Molecular Geriatrics, Uppsala University, Uppsala, Sweden.
Lars LindMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Cecilia C M LindgrenWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Elmo MannarinoDepartment of Clinical and Experimental Medicine, Internal Medicine, Angiology and Arteriosclerosis Diseases, University of Perugia, Perugia, Italy.
Dennis O Mook-KanamoriDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands.
Andrew P MorrisWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Department of Biostatistics, University of Liverpool, Liverpool, UK.
Renée de MutsertDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Rainer RauramaaFoundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland; Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
Peter Saliba-GustafssonCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Bengt SennbladCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Dept of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Sweden.
Andries J SmitDepartment of Medicine, University Medical Center Groningen, Groningen, The Netherlands; Department of Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Ann-Christine SyvänenDepartment of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Elena TremoliDipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy; Centro Cardiologico Monzino, IRCCS, Milan, Italy.
Fabrizio VegliaCentro Cardiologico Monzino, IRCCS, Milan, Italy.
Björn ZetheliusDepartment of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden.
Hanna M BjörckCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Johan G ErikssonDepartment of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; National Institute for Health and Welfare, Finland; Folkhälsan Research Center, Helsinki, Finland.
Albert HofmanDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, The Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Oscar H FrancoDepartment of Epidemiology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
Hugh WatkinsWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
J Wouter JukemaDepartment of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
Jose C FlorezDiabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Programs in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Cambridge, MA, USA.
Nicholas J WarehamMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
James B MeigsPrograms in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Cambridge, MA, USA; General Medicine Division, Massachusetts General Hospital, Boston, MA, USA.
Erik IngelssonDepartment of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Damiano BaldassarreDipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Italy.
Anders HamstenCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
IMPROVE study group
Karolinska Institutet · SEUppsala University · SECentre for Human Genetics · GBLeiden University Medical Center · NLErasmus MC · NLUniversity of Cambridge · GBUniversity of Helsinki · FIBoston University · USBroad Institute · USUniversity of Milan · ITAssistance Publique – Hôpitaux de Paris · FRCentro Cardiologico Monzino · ITHarvard University · USKarolinska University Hospital · SEKuopio University Hospital · FIUniversity College London · GBUniversity Medical Center Groningen · NLUniversity of Eastern Finland · FIUniversity of Perugia · IT

Funding

Rare Sequence Variation and Diabetes Quantitative TraitsU01DK078616 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2015 to 2019
$3.6M
Beyond GWAS of insulin resistance: An integrated approach to translate genetic association to functionR01DK106236 · NIDDK · STANFORD UNIVERSITY · PI KNOWLES, JOSHUA WILEY · 2016 to 2020
$2.4M
Epidemiology of Precursors to Type 2 DiabetesK24DK080140 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI MEIGS, JAMES B · 2007 to 2016
$1.9M
Causal associations of circulating biomarkers with cardiovascular diseaseR01HL135313 · NHLBI · STANFORD UNIVERSITY · PI INGELSSON, ERIK · 2017 to 2019
$1.6M
British Heart Foundation RG/08/008/25291Medical Research Council MC_U106179471Medical Research Council MC_UU_12015/1NHLBI NIH HHS R01 HL135313NIDDK NIH HHS K24 DK080140NIDDK NIH HHS R01 DK106236NIDDK NIH HHS U01 DK078616
6 · The paper itself

Abstract

BACKGROUND AND

aimsIncreased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling.

methodsWe studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants.

resultsWe identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMT

conclusionsWe identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT.

Indexed as

Mendelian Randomization AnalysisPolymorphism, Single NucleotideAsymptomatic DiseasesCarotid Artery DiseasesCarotid Intima-Media ThicknessChromosomes, Human, Pair 15EuropeFemaleGene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseHumansLinear ModelsMalePhenotypeProinsulinProinsulinAtherosclerosisGenetic variantsIntima-media-thicknessMendelian randomisationProinsulinSingle nucleotide polymorphisms

Identifiers

PMID29040868
PMCPMC5679136
OpenAlexW2757783262

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.