Sepsis is a life-threatening clinical syndrome of physiological, pathological, and biochemical abnormalities caused by a dysregulated host response to an infection. Sepsis is accompanied by multiple organ dysfunction and is the leading cause of mortality in adults in Intensive Care Units (ICU). There is a lack of targeted therapies or effective methods for predicting prognosis or risk of death among these patients.
Since sepsis is a complex and heterogeneous disease, there is a lack of susceptibility GWAS in the literature to date. However, candidate genes studies and GWAS of sepsis mortality have associated common variants near genes involved in host defence, among others.
We conducted a two-staged GWAS (1; https://www.medrxiv.org/content/10.1101/2022.05.06.22274756v1) involving GEN-SEP network patients (2) in the first stage and MESSI ICU patients (3) in the second stage. For the first stage, we performed a meta-analysis of the GEN-SEP network patients recruited at two different periods. The first stage analyzed a total of 687 European sepsis patients (506 survivors and 181 deceased) and nearly 7.5 million imputed variants. The second stage consisted on a follow-up of prioritized variants from the first stage on 2063 ICU sepsis patients.
Figure 1. Sample sizes for genome-wide analyses in the first stage.
To allow the wider research community to access the effect sizes and significance for genetic variants on a genome-wide scale, the variant summary data from the first stage of the study by Hernandez-Beeftink T et al. (1)(https://www.medrxiv.org/content/10.1101/2022.05.06.22274756v1) (filesize 476 MB) can be accessed after an internal assessment of formal requests are received.
No individual level data will be made available. Granted requests will have access to a file with the GWAS meta-analysis variant summary data with information for the following descriptors:
- CHR.
- POS. According to GRCh37/hg19 reference
- SNP.
- A1_REF. Reference allele
- A2_ALT. Effect allele
- PVALUE. This is the p value from the meta-analysis
- COEF. This is the beta from the meta-analysis
- SECOEF. This is the standard error from the meta-analysis
- Model. Based on the significance of Cochran's Q, the meta-analysis shows the result of the fixed effects model (FE) or the random effects model (RE2)(4)
- MAF. Minor allele frequency taken from the first period of stage 1
Requesters should contact cflores [at] ull [dot] edu [dot] es for requesting access to the data and review the request. An email with the instructions for data accessing will be obtained in response.
Requesters should provide, at least, a signed document including the following information: full name and title of the PI, affiliation, and a brief description of the project and the aims where the data is to be used.
The document should explicitly state that the data requester also agrees to: use the data only as part of that indicated research, not redistribute the data outside the project without permission, acknowledge the provenance of the data in any dissemination of results.
A template document for the request is here.
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Hernandez-Beeftink T, Guillen-Guio B, Lorenzo-Salazar JM, Corrales A, Suarez-Pajes E, Feng R, Rubio-Rodríguez LA, Paynton ML, Cruz-Guerrero R, García-Laorden MI, Prieto-González M, Rodríguez-Pérez A, Carriedo D, Blanco J, Ambrós A, González-Higueras E, Espinosa E, Muriel A, Tamayo E, Martin MM, Lorente L, Domínguez D, García de Lorenzo A, Giannini HM, Reilly JP, Jones TK, Añón JM, Soro M, Carracedo A, Wain LV, Meyer NJ, Villar J, and Carlos Flores on behalf of the Genetics of Sepsis (GEN-SEP) Network. A Genome-Wide Association Study of Survival in Patients with Sepsis. medRxiv 2022.05.06.22274756v1; doi: https://doi.org/10.1101/2022.05.06.22274756.
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Guillen-Guio B, Lorenzo-Salazar JM, Ma SF, Hou PC, Hernandez-Beeftink T, Corrales A, García-Laorden MI, Jou J, Espinosa E, Muriel A, Domínguez D, Lorente L, Martín MM, Rodríguez-Gallego C, Solé-Violán J, Ambrós A, Carriedo D, Blanco J, Añón JM, Reilly JP, Jones TK, Ittner CA, Feng R, Schöneweck F, Kiehntopf M, Noth I, Scholz M, Brunkhorst FM, Scherag A, Meyer NJ, Villar J, Flores C. Sepsis-associated acute respiratory distress syndrome in individuals of European ancestry: a genome-wide association study. Lancet Respir Med. 2020 Mar;8(3):258-266. doi: https://doi.org/10.1016/S2213-2600(19)30368-6.
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Reilly JP, Meyer NJ, Shashaty MG, Feng R, Lanken PN, Gallop R, et al. ABO blood type A is associated with increased risk of ARDS in whites following both major trauma and severe sepsis. Chest. 2014;145(4):753–61. doi: https://doi.org/10.1186/s13054-016-1244-2
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Han B, Eskin E. Random-effects model aimed at discovering associations in meta-analysis of genome-wide association studies. Am J Hum Genet. 2011 May 13;88(5):586-98. doi: https://doi.org/10.1016/j.ajhg.2011.04.014.
