Evidence map›Paper›PMID 40168842›Full record

SynthesisEBioMedicine2025

Genetic association studies in critically ill patients: a systematic review.

Wenbo Zhang, Nam Nguyen-Hoang, Sean C S Rivrud, Anne-Fleur Zandbergen, Yalan Yan, Eline G M Cox, Eva Suarez-Pajes, Amanda Y Chong, Alexander J Mentzer, Carlos Flores and 3 more

Abstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Review
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

13 authors.

Wenbo ZhangDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, 9713 GZ, Groningen, the Netherlands; Department of Critical Care, University of Groningen, University Medical Center Groningen, 9713 GZ, Groningen, the Netherlands.
Nam Nguyen-HoangDepartment of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA.
Sean C S RivrudDepartment of Critical Care, University of Groningen, University Medical Center Groningen, 9713 GZ, Groningen, the Netherlands.
Anne-Fleur ZandbergenDepartment of Critical Care, University of Groningen, University Medical Center Groningen, 9713 GZ, Groningen, the Netherlands.
Yalan YanDepartment of Critical Care Medicine, The Second Affiliated Hospital of the Chinese University of Hong Kong (Shenzhen) (Longgang District People's Hospital of Shenzhen), Shenzhen, 5l8100, China.
Eline G M CoxDepartment of Critical Care, University of Groningen, University Medical Center Groningen, 9713 GZ, Groningen, the Netherlands.
Eva Suarez-PajesResearch Unit, Hospital Universitario Nuestra Señora de Candelaria, Instituto de Investigación Sanitaria de Canarias (IISC), 38010, Santa Cruz de Tenerife, Spain.
Amanda Y ChongThe Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Alexander J MentzerThe Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
Carlos FloresResearch Unit, Hospital Universitario Nuestra Señora de Candelaria, Instituto de Investigación Sanitaria de Canarias (IISC), 38010, Santa Cruz de Tenerife, Spain; CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029, Madrid, Spain; Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), 38600, Santa Cruz de Tenerife, Spain; Faculty of Health Sciences, University of Fernando Pessoa Canarias, 35450, Las Palmas de Gran Canaria, Spain.
Gerton LunterDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, 9713 GZ, Groningen, the Netherlands.
Frederik KeusDepartment of Critical Care, University of Groningen, University Medical Center Groningen, 9713 GZ, Groningen, the Netherlands.
Harold SniederDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, 9713 GZ, Groningen, the Netherlands. Electronic address: h.snieder@umcg.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCritical illness is complex, and genetic research holds the potential to uncover underlying disease mechanisms. However, existing research results have not been systematically summarized. This study aims to compile all genetic association studies in critically ill patients and assess their risks of bias.

methodsWe systematically reviewed PubMed, EMBASE, and the Cochrane Library (PROSPERO protocol: CRD42021209744) and conducted a bias risk assessment of identified studies using a newly developed risk-of-bias assessment tool for genetic association studies. We compiled all significant single nucleotide polymorphisms (SNPs) from the studies identified in our systematic review and conducted a lookup in the results of two genome-wide association studies (GWASs) in critically ill patients.

findingsWe identified a total of 61 studies that evaluated genetic variants with various traits in adult intensive care patients, encompassing a total of 126 genetic loci and focussing on six clustered critical care-related traits. Assessment of the risk of bias across these studies revealed that 97% of the studies demonstrated some concerns or high risk of bias and only two studies (3%, both GWAS), had an overall low risk of bias. Only two significantly associated SNPs emerged from the two studies assessed to have a low risk of bias. One SNP (rs4957796) in FER was associated with 28-day survival (p = 3.4 × 10

interpretationOur systematic review underscored a deficiency in high-quality genetic research in critical care medicine. The detected gaps emphasize an urgent need for additional rigorous genetic association studies that are preferably genome-wide, to enhance our understanding of the underlying mechanisms of critical illness.

fundingWenbo Zhang was financially supported by a grant from the China Scholarship Council (File no. 202006210041). Carlos Flores was funded by Instituto de Salud Carlos III (PI23/00980 and CB06/06/1088) and co-financed by the European Regional Development Fund, "A way of making Europe" from the European Union; and the agreement OA23/043 with Instituto Tecnológico y de Energías Renovables (ITER) to strengthen scientific and technological education, training, research, development and scientific innovation in genomics, epidemiological surveillance based on massive sequencing, personalized medicine, and biotechnology. Eva Suarez-Pajes was financially supported by Agencia Canaria de Investigación, Innovación y Sociedad de la Información de la Consejería de Economía, Conocimiento y Empleo y por el Fondo Social Europeo (FSE) Programa Operativo Integrado de Canarias 2014-2020, Eje 3 Tema Prioritario 74 (85%) (TESIS2022010042).

Indexed as

Critical IllnessGenetic Association StudiesGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideCandidate gene studyCritically ill patientsGeneticsGenome-wide association studyIntensive care

Identifiers

PMID40168842
PMCPMC11999069

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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.