Beyond single-marker analyses: mining whole genome scans for insights into treatment responses in severe sepsis.

Man M, Close SL, Shaw AD, Bernard GR, Douglas IS, Kaner RJ, Payen D, Vincent JL, Fossceco S, Janes JM, Leishman AG, O'Brien L, Williams MD, Garcia JG
Pharmacogenomics J. 2013 13 (3): 218-26

PMID: 22310353 · DOI:10.1038/tpj.2012.1

Management of severe sepsis, an acute illness with high morbidity and mortality, suffers from the lack of effective biomarkers and largely empirical predictions of disease progression and therapeutic responses. We conducted a genome-wide association study using a large randomized clinical trial cohort to discover genetic biomarkers of response to therapy and prognosis utilizing novel approaches, including combination markers, to overcome limitations of single-marker analyses. Sepsis prognostic models were dominated by clinical variables with genetic markers less informative. In contrast, evidence for gene-gene interactions were identified for sepsis treatment responses with genetic biomarkers dominating models for predicting therapeutic responses, yielding candidates for replication in other cohorts.

MeSH Terms (12)

Biomarkers, Pharmacological Disease Progression Epistasis, Genetic Genetic Markers Genome-Wide Association Study Humans Polymorphism, Single Nucleotide Prognosis Protein C Randomized Controlled Trials as Topic Recombinant Proteins Sepsis

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