Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study  Dr Anna Rautanen, PhD, Tara C Mills, DPhil, Anthony C Gordon, MD, Paula Hutton, PG Cert, Michael Steffens, MD, Rosamond Nuamah, BSc, Prof Jean-Daniel Chiche, MD, Tom Parks, MB, Stephen J Chapman, DM, Emma E Davenport, MBiochem, Katherine S Elliott, PhD, Prof Julian Bion, MD, Peter Lichtner, PhD, Prof Thomas Meitinger, MD, Prof Thomas F Wienker, MD, Prof Mark J Caulfield, MD, Charles Mein, PhD, Frank Bloos, MD, Ilona Bobek, PhD, Paolo Cotogni, MD, Vladimir Sramek, MD, Silver Sarapuu, MD, Makbule Kobilay, Prof V Marco Ranieri, MD, Prof Jordi Rello, PhD, Gonzalo Sirgo, MD, Yoram G Weiss, MD, Stefan Russwurm, MD, E Marion Schneider, PhD, Prof Konrad Reinhart, MD, Paul A H Holloway, PhD, Prof Julian C Knight, DPhil, Chris S Garrard, MD, Prof James A Russell, MD, Prof Keith R Walley, MD, Prof Frank Stüber, MD, Prof Adrian V S Hill, DPhil, Prof Charles J Hinds, FRCP  The Lancet Respiratory Medicine  Volume 3, Issue 1, Pages 53-60 (January 2015) DOI: 10.1016/S2213-2600(14)70290-5 Copyright © 2015 Rautanen et al. Open Access article distributed under the terms of CC-BY-NC-SA Terms and Conditions

Figure 1 Patient cohorts, samples, genotyping, and analysis SNP=single nucleotide polymorphism. HRMA=high-resolution melting curve analysis. QC=quality control. The Lancet Respiratory Medicine 2015 3, 53-60DOI: (10.1016/S2213-2600(14)70290-5) Copyright © 2015 Rautanen et al. Open Access article distributed under the terms of CC-BY-NC-SA Terms and Conditions

Figure 2 Manhattan plot for the meta-analysis of 28 day survival in patients with sepsis due to pneumonia (additive model) SNPs with minor allele frequency higher than 2%, information value higher than 0·8, and Hardy-Weinberg equilibrium p higher than 1×10−10 are included (5 888 277 SNPs in total). The region including the FER gene is highlighted in red. The Lancet Respiratory Medicine 2015 3, 53-60DOI: (10.1016/S2213-2600(14)70290-5) Copyright © 2015 Rautanen et al. Open Access article distributed under the terms of CC-BY-NC-SA Terms and Conditions

Figure 3 Regional association plot for the chromosome 5 locus (rs4957796) in the meta-analysis of 28 day survival in patients with sepsis due to pneumonia (additive model) Colours indicate the correlation (r2 in CEU [Utah residents with northern or western European ancestry] 1000 Genomes data) with the top SNP rs4957796. The Lancet Respiratory Medicine 2015 3, 53-60DOI: (10.1016/S2213-2600(14)70290-5) Copyright © 2015 Rautanen et al. Open Access article distributed under the terms of CC-BY-NC-SA Terms and Conditions

Figure 4 Forest plot for FER SNP rs4957796 in separate cohorts and combined in the meta-analysis of 28 day survival in patients with sepsis due to pneumonia (additive model) ORs (95% CIs) and number of deaths and C and T allele counts in non-survivors and survivors are shown. The Lancet Respiratory Medicine 2015 3, 53-60DOI: (10.1016/S2213-2600(14)70290-5) Copyright © 2015 Rautanen et al. Open Access article distributed under the terms of CC-BY-NC-SA Terms and Conditions

Figure 5 Cumulative percentage death rates in patients with sepsis caused by pneumonia according to FER rs4957796 genotype (A) All cohorts combined followed up until 28 days from ICU admission. (B) Directly genotyped GenOSept/GAinS discovery and additional GAinS cohorts followed up until 6 months from ICU admission. The Lancet Respiratory Medicine 2015 3, 53-60DOI: (10.1016/S2213-2600(14)70290-5) Copyright © 2015 Rautanen et al. Open Access article distributed under the terms of CC-BY-NC-SA Terms and Conditions