Evidence map›Paper›PMID 37940228›Full record

ArticleJournal of the American College of Cardiology2023

Plasma Proteomics to Identify Drug Targets for Ischemic Heart Disease.

Mohsen Mazidi, Neil Wright, Pang Yao, Christiana Kartsonaki, Iona Y Millwood, Hannah Fry, Saredo Said, Alfred Pozarickij, Pei Pei, Yiping Chen and 18 more

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

Article in Journal of the American College of Cardiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 2 pooled it
11.3field-weighted citation impact, top 1% 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

31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.

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  18. Sex differences in proteomics of cardiovascular disease -International journal of cardiology. Heart & vasculature · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors at 4 institutions in 2 countries.

Mohsen MazidiClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Neil WrightClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Pang YaoClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Christiana KartsonakiClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Medical Research Council Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Iona Y MillwoodClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Medical Research Council Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Hannah FryClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Medical Research Council Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Saredo SaidClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Alfred PozarickijClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Pei PeiPeking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China.
Yiping ChenClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Medical Research Council Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Daniel AveryClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Huaidong DuClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Medical Research Council Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Dan Valle SchmidtClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Ling YangClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Medical Research Council Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Jun LvPeking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China; Key Laboratory of Epidemiology of Major (Peking University), Ministry of Education, Beijing, China.
Canqing YuPeking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China; Key Laboratory of Epidemiology of Major (Peking University), Ministry of Education, Beijing, China.
Junshi ChenChina National Center for Food Risk Assessment, Beijing, China.
Michael HillClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Medical Research Council Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Michael V HolmesClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Joanna M M HowsonNovo Nordisk Research Centre, Oxford, United Kingdom.
Richard PetoClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Rory CollinsClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Derrick A BennettClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Medical Research Council Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Robin G WaltersClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Medical Research Council Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Liming LiPeking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China; Key Laboratory of Epidemiology of Major (Peking University), Ministry of Education, Beijing, China.
Robert ClarkeClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. Electronic address: robert.clarke@ndph.ox.ac.uk.
Zhengming ChenClinical Trial Service Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Medical Research Council Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. Electronic address: zhengming.chen@ndph.ox.ac.uk.
China Kadoorie Biobank Collaborative Group
University of Oxford · GBChina National Center for Food Safety Risk Assessment · CNPeking University · CNNovo Nordisk (United Kingdom) · GB

Funding

Cancer Research UK 29186Medical Research Council MC_PC_14135Medical Research Council MC_UU_00017/1Medical Research Council MC_UU_12026/2Wellcome Trust 212946/Z/18/Z
6 · The paper itself

Abstract

backgroundIntegrated analyses of plasma proteomic and genetic markers in prospective studies can clarify the causal relevance of proteins and discover novel targets for ischemic heart disease (IHD) and other diseases.

objectivesThe purpose of this study was to examine associations of proteomics and genetics data with IHD in population studies to discover novel preventive treatments.

methodsWe conducted a nested case-cohort study in the China Kadoorie Biobank (CKB) involving 1,971 incident IHD cases and 2,001 subcohort participants who were genotyped and free of prior cardiovascular disease. We measured 1,463 proteins in the stored baseline samples using the OLINK EXPLORE panel. Cox regression yielded adjusted HRs for IHD associated with individual proteins after accounting for multiple testing. Moreover, cis-protein quantitative loci (pQTLs) identified for proteins in genome-wide association studies of CKB and of UK Biobank were used as instrumental variables in separate 2-sample Mendelian randomization (MR) studies involving global CARDIOGRAM+C4D consortium (210,842 IHD cases and 1,378,170 controls).

resultsOverall 361 proteins were significantly associated at false discovery rate <0.05 with risk of IHD (349 positively, 12 inversely) in CKB, including N-terminal prohormone of brain natriuretic peptide and proprotein convertase subtilisin/kexin type 9. Of these 361 proteins, 212 had cis-pQTLs in CKB, and MR analyses of 198 variants in CARDIOGRAM+C4D identified 13 proteins that showed potentially causal associations with IHD. Independent MR analyses of 307 cis-pQTLs identified in Europeans replicated associations for 4 proteins (FURIN, proteinase-activated receptor-1, Asialoglycoprotein receptor-1, and matrix metalloproteinase-3). Further downstream analyses showed that FURIN, which is highly expressed in endothelial cells, is a potential novel target and matrix metalloproteinase-3 a potential repurposing target for IHD.

conclusionsIntegrated analyses of proteomic and genetic data in Chinese and European adults provided causal support for FURIN and multiple other proteins as potential novel drug targets for treatment of IHD.

Indexed as

FurinMyocardial IschemiaAdultCase-Control StudiesCohort StudiesEndothelial CellsGenome-Wide Association StudyHumansMatrix MetalloproteinasesProspective StudiesProteomicsRisk FactorsFurinMatrix Metalloproteinasesdiverse populationsdrug targetgeneticsischemic heart diseaseMendelian randomizationplasma proteomicsprospective studies

Identifiers

PMID37940228
PMCPMC10641761
OpenAlexW4388407396

What OpenQuestion 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 OpenQuestion graph.