Evidence map›Paper›PMID 35772218›Full record

ArticleEBioMedicine2022

Multi-ancestry Mendelian randomization of omics traits revealing drug targets of COVID-19 severity.

Jie Zheng, Yuemiao Zhang, Huiling Zhao, Yi Liu, Denis Baird, Mohd Anisul Karim, Maya Ghoussaini, Jeremy Schwartzentruber, Ian Dunham, Benjamin Elsworth and 8 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 8% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 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

18 authors at 7 institutions in 2 countries.

Jie ZhengDepartment of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; MRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom. Electronic address: jie.zheng@bristol.ac.uk.
Yuemiao ZhangRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People's Republic of China.
Huiling ZhaoMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom.
Yi LiuMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom.
Denis BairdMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom.
Mohd Anisul KarimWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, United Kingdom; Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, United Kingdom.
Maya GhoussainiWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, United Kingdom; Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, United Kingdom.
Jeremy SchwartzentruberWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, United Kingdom; Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, United Kingdom.
Ian DunhamWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SA, United Kingdom; Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, United Kingdom; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, United Kingdom.
Benjamin ElsworthMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom.
Katherine RobertsBristol Medical School, University of Bristol, 5 Tyndall Avenue, Bristol, BS8 1UD, United Kingdom.
Hannah ComptonBristol Medical School, University of Bristol, 5 Tyndall Avenue, Bristol, BS8 1UD, United Kingdom.
Felix Miller-MolloyBristol Medical School, University of Bristol, 5 Tyndall Avenue, Bristol, BS8 1UD, United Kingdom.
Xingzi LiuRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People's Republic of China.
Lin WangDepartment of Microbiology and Infectious Disease Centre, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing, China.
Hong ZhangRenal Division, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People's Republic of China.
George Davey SmithMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom; NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol, United Kingdom.
Tom R GauntMRC Integrative Epidemiology Unit (IEU), Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom; NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol, United Kingdom. Electronic address: tom.gaunt@bristol.ac.uk.
University of Bristol · GBMinistry of Education of the People's Republic of China · CNWellcome Sanger Institute · GBUniversity Hospitals Bristol NHS Foundation Trust · GBEuropean Bioinformatics Institute · GBPeking University · CNShanghai Jiao Tong University · CN

Funding

Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MC_UU_00011/1Medical Research Council MC_UU_00011/4Wellcome Trust
6 · The paper itself

Abstract

backgroundRecent omic studies prioritised several drug targets associated with coronavirus disease 2019 (COVID-19) severity. However, little evidence was provided to systematically estimate the effect of drug targets on COVID-19 severity in multiple ancestries.

methodsIn this study, we applied Mendelian randomization (MR) and colocalization approaches to understand the putative causal effects of 16,059 transcripts and 1608 proteins on COVID-19 severity in European and effects of 610 proteins on COVID-19 severity in African ancestry. We further integrated genetics, clinical and literature evidence to prioritise drug targets. Additional sensitivity analyses including multi-trait colocalization and phenome-wide MR were conducted to test for MR assumptions.

findingsMR and colocalization prioritized four protein targets, FCRL3, ICAM5, ENTPD5 and OAS1 that showed effect on COVID-19 severity in European ancestry. One protein target, SERPINA1 showed a stronger effect in African ancestry but much weaker effect in European ancestry (odds ratio [OR] in Africans=0.369, 95%CI=0.203 to 0.668, P = 9.96 × 10

interpretationOur study identified six proteins as showing putative causal effects on COVID-19 severity. OAS1 and SERPINA1 were targets of existing drugs in trials as potential COVID-19 treatments. ICAM1, ICAM5 and FCRL3 are related to the immune system. Across the six targets, OAS1 has no reliable instrument in African ancestry; SERPINA1, FCRL3, ICAM5 and ENTPD5 showed a different level of putative causal evidence in European and African ancestries, which highlights the importance of more powerful ancestry-specific GWAS and value of multi-ancestry MR in informing the effects of drug targets on COVID-19 across different populations. This study provides a first step towards clinical investigation of beneficial and adverse effects of COVID-19 drug targets.

fundingNo.

Indexed as

COVID-19COVID-19 Drug TreatmentMendelian Randomization AnalysisGenome-Wide Association StudyHumansOdds RatioPhenotypePolymorphism, Single NucleotideColocalizationCOVID-19 severityDrug targetsMendelian randomizationMulti-ancestry

Identifiers

PMID35772218
PMCPMC9235320
OpenAlexW4283779419

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.