• 作者：André ; Scherag^a ; ^b ; ¹ ; ^{andre.scherag@med.uni-jena.de" class="auth_mail" title="E-mail the corresponding author} ; Franziska Schö ; neweck^a ; ^b ; ¹ ; Miriam Kesselmeier^a ; ^b ; Stefan Taudien^a ; ^c ; Matthias Platzer^c ; Marius Felder^c ; Christoph Sponholz^a ; ^c ; ^d ; Anna Rautanen^e ; ² ; Adrian V.S. Hill^e ; ² ; Charles J. Hinds^f ; ² ; Hamid Hossain^g ; ³ ; Norbert Suttorp^h ; ³ ; Oliver Kurzai^a ; ⁱ ; ^j ; Hortense Slevogt^a ; ^j ; Evangelos J. Giamarellos-Bourboulis^a ; ^k ; ⁴ ; Apostolos Armaganidis^l ; Evelyn Trips^m ; Markus Scholzⁿ ; ^o ; ¹ ; Frank M. Brunkhorst^a ; ^p ; ^q ; ¹
• 关键词：Sepsis ; Host response ; Genome-wide association study ; Mortality ; Exome
• 刊名：EBioMedicine
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：12
• 期：Complete
• 页码：239-246
• 全文大小：518 K

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A low frequency missense variant in VPS13A on chromosome 9q21.2 was associated with 28 day mortality after sepsis

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A frequent intronic variant in CRISPLD2 was also supported and was reported to be associated with procalcitonin levels

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Similarly supported was an intergenic frequent variant on chromosome13q21.33 – a region related to chronic kidney disease

Sepsis is the dysregulated host response to an infection which leads to life-threatening organ dysfunction that is known to vary by host genomic factors. However, the detection of genetic variants related to sepsis outcomes has been challenging so far. We conducted a discovery genome-wide association study (GWAS) in 740 adult patients with sepsis looking for variants that vary with 28 day mortality. We followed-up our best findings by additional GWAS and exome sequencing data in 3544 adult patients and report three regions including the genes VPS13A and CRISPLD2 that were supported by our data and external biological evidence.