A genome-wide association study of survival in patients with sepsis.
28 days
Genome-wide association study
Genomics
Outcome
Sepsis
Journal
Critical care (London, England)
ISSN: 1466-609X
Titre abrégé: Crit Care
Pays: England
ID NLM: 9801902
Informations de publication
Date de publication:
05 Nov 2022
05 Nov 2022
Historique:
received:
20
07
2022
accepted:
17
10
2022
entrez:
6
11
2022
pubmed:
6
11
2022
medline:
9
11
2022
Statut:
epublish
Résumé
Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide association study (GWAS) of 28-day survival in adult patients with sepsis. This study was conducted in two stages. The first stage was performed on 687 European sepsis patients from the GEN-SEP network and 7.5 million imputed variants. Association testing was conducted with Cox regression models, adjusting by sex, age, and the main principal components of genetic variation. A second stage focusing on the prioritized genetic variants was performed on 2,063 ICU sepsis patients (1362 European Americans and 701 African-Americans) from the MESSI study. A meta-analysis of results from the two stages was conducted and significance was established at p < 5.0 × 10 We identified three independent low-frequency variants associated with reduced 28-day sepsis survival, including a missense variant in SAMD9 (hazard ratio [95% confidence interval] = 1.64 [1.37-6.78], p = 4.92 × 10 We performed the first GWAS of 28-day sepsis survival and identified novel variants associated with reduced survival. Larger sample size studies are needed to better assess the genetic effects in sepsis survival and to validate the findings.
Sections du résumé
BACKGROUND
Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide association study (GWAS) of 28-day survival in adult patients with sepsis.
METHODS
This study was conducted in two stages. The first stage was performed on 687 European sepsis patients from the GEN-SEP network and 7.5 million imputed variants. Association testing was conducted with Cox regression models, adjusting by sex, age, and the main principal components of genetic variation. A second stage focusing on the prioritized genetic variants was performed on 2,063 ICU sepsis patients (1362 European Americans and 701 African-Americans) from the MESSI study. A meta-analysis of results from the two stages was conducted and significance was established at p < 5.0 × 10
FINDINGS
We identified three independent low-frequency variants associated with reduced 28-day sepsis survival, including a missense variant in SAMD9 (hazard ratio [95% confidence interval] = 1.64 [1.37-6.78], p = 4.92 × 10
INTERPRETATION
We performed the first GWAS of 28-day sepsis survival and identified novel variants associated with reduced survival. Larger sample size studies are needed to better assess the genetic effects in sepsis survival and to validate the findings.
Identifiants
pubmed: 36335405
doi: 10.1186/s13054-022-04208-5
pii: 10.1186/s13054-022-04208-5
pmc: PMC9637317
doi:
Substances chimiques
SAMD9 protein, human
0
Intracellular Signaling Peptides and Proteins
0
Types de publication
Meta-Analysis
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
341Subventions
Organisme : NHLBI NIH HHS
ID : K24 HL155804
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL161196
Pays : United States
Informations de copyright
© 2022. The Author(s).
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