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Reference: Scherag, A, Schöneweck, F, Kesselmeier, M et al., (2016). Genetic factors of the disease course after sepsis: a genome-wide study for 28 day mortality. EBioMedicine.Citable link to this page:

 

Genetic factors of the disease course after sepsis: a genome-wide study for 28 day mortality

Abstract: Sepsis is the dysregulated host response to an infection which leads to life-threatening organ dysfunction that varies by host genomic factors. We conducted a genome-wide association study (GWAS) in 740 adult septic patients and focused on 28day mortality as outcome. Variants with suggestive evidence for an association (p≤10(-5)) were validated in two additional GWA studies (n=3470) and gene coding regions related to the variants were assessed in an independent exome sequencing study (n=74). In the discovery GWAS, we identified 243 autosomal variants which clustered in 14 loci (p≤10(-5)). The best association signal (rs117983287; p=8.16×10(-8)) was observed for a missense variant located at chromosome 9q21.2 in the VPS13A gene. VPS13A was further supported by additional GWAS (p=0.03) and sequencing data (p=0.04). Furthermore, CRISPLD2 (p=5.99×10(-6)) and a region on chromosome 13q21.33 (p=3.34×10(-7)) were supported by both our data and external biological evidence. We found 14 loci with suggestive evidence for an association with 28day mortality and found supportive, converging evidence for three of them in independent data sets. Elucidating the underlying biological mechanisms of VPS13A, CRISPLD2, and the chromosome 13 locus should be a focus of future research activities.

Publication status:In pressPeer Review status:Peer reviewedVersion:Publisher's versionDate of acceptance:2016-08-27Notes:Copyright © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Bibliographic Details

Publisher: Elsevier

Publisher Website: http://www.elsevier.com/

Journal: EBioMedicinesee more from them

Publication Website: http://www.ebiomedicine.com/

Volume: 12

Issue: October 2016

Extent: 239–246

Issue Date: 14 September 2016

pages:239–246Identifiers

Doi: https://doi.org/10.1016/j.ebiom.2016.08.043

Issn: 2352-3964

Uuid: uuid:73d54cc5-b034-40be-8173-59c1a30133a9

Urn: uri:73d54cc5-b034-40be-8173-59c1a30133a9

Pubs-id: pubs:646041 Item Description

Type: journal-article;

Language: eng

Version: Publisher's versionKeywords: exome genome-wide association study host response mortality sepsis

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Author: Scherag, A - - - Schöneweck, F - - - Kesselmeier, M - - - Taudien, S - - - Platzer, M - - - Felder, M - - - Sponholz, C - - - Ra

Source: https://ora.ox.ac.uk/objects/uuid:73d54cc5-b034-40be-8173-59c1a30133a9



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