A genome-wide association study of survival in patients with sepsis.

Autor: Hernandez-Beeftink T; Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Carretera del Rosario S/N, Santa Cruz de Tenerife, Spain.; Research Unit, Hospital Universitario de Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria, Spain., Guillen-Guio B; Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Carretera del Rosario S/N, Santa Cruz de Tenerife, Spain.; Department of Health Sciences, University of Leicester, Leicester, UK., Lorenzo-Salazar JM; Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain., Corrales A; Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Carretera del Rosario S/N, Santa Cruz de Tenerife, Spain.; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain., Suarez-Pajes E; Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Carretera del Rosario S/N, Santa Cruz de Tenerife, Spain., Feng R; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA., Rubio-Rodríguez LA; Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain., Paynton ML; Department of Health Sciences, University of Leicester, Leicester, UK., Cruz R; Genomic Medicine Group, Biomedical Research Center of Rare Diseases (CIBERER), University of Santiago de Compostela, Santiago de Compostela, Spain., García-Laorden MI; Research Unit, Hospital Universitario de Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria, Spain.; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain., Prieto-González M; Intensive Care Unit, Complejo Asistencial Universitario de Palencia, Palencia, Spain., Rodríguez-Pérez A; Department of Anesthesiology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain.; Department of Medical and Surgical Sciences, University of Las Palmas de Gran Canaria, Gran Canaria, Spain., Carriedo D; Intensive Care Unit, Complejo Hospitalario Universitario de León, León, Spain., Blanco J; Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain.; Intensive Care Unit, Hospital Universitario Rio Hortega, Valladolid, Spain., Ambrós A; Intensive Care Unit, Hospital General de Ciudad Real, Ciudad Real, Spain., González-Higueras E; Intensive Care Unit, Hospital Virgen de la Luz, Cuenca, Spain., Espinosa E; Department of Anesthesiology, Hospital Universitario N.S. de Candelaria, Santa Cruz de Tenerife, Spain., Muriel A; Intensive Care Unit, Hospital Universitario Rio Hortega, Valladolid, Spain., Tamayo E; CIBER de Enfermedades Infecciosas, Department of Anesthesiology and Resuscitation, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.; Departamento de Cirugía, Facultad de Medicina, Universidad de Valladolid, Valladolid, Spain., Martin MM; Intensive Care Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain., Lorente L; Intensive Care Unit, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain., Domínguez D; Department of Anesthesiology, Hospital Universitario N.S. de Candelaria, Santa Cruz de Tenerife, Spain., de Lorenzo AG; Intensive Care Unit, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain., Giannini HM; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA., Reilly JP; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA., Jones TK; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA., Añón JM; Intensive Care Unit, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain., Soro M; Department of Anesthesiology, Hospital Clinico Universitario de Valencia, Valencia, Spain., Carracedo Á; Genomic Medicine Group, Biomedical Research Center of Rare Diseases (CIBERER), University of Santiago de Compostela, Santiago de Compostela, Spain.; Genomic Medicine Group, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.; Galician Foundation of Genomic Medicine, Foundation of Health Research Institute of Santiago de Compostela (FIDIS), SERGAS, Santiago de Compostela, Spain., Wain LV; Department of Health Sciences, University of Leicester, Leicester, UK.; Leicester Respiratory Biomedical Research, Centre, National Institute for Health Research, Glenfield Hospital, Leicester, UK., Meyer NJ; Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA., Villar J; Research Unit, Hospital Universitario de Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria, Spain.; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada., Flores C; Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Carretera del Rosario S/N, Santa Cruz de Tenerife, Spain. cflores@ull.edu.es.; Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain. cflores@ull.edu.es.; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain. cflores@ull.edu.es.; Facultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain. cflores@ull.edu.es.
Jazyk: angličtina
Zdroj: Critical care (London, England) [Crit Care] 2022 Nov 05; Vol. 26 (1), pp. 341. Date of Electronic Publication: 2022 Nov 05.
DOI: 10.1186/s13054-022-04208-5
Abstrakt: 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 -8 . Whole-blood transcriptomic, functional annotations, and sensitivity analyses were evaluated on the identified genes and variants.
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 -8 ). SAMD9 encodes a possible mediator of the inflammatory response to tissue injury.
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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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