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

TitleBeyond single-marker analyses: mining whole genome scans for insights into treatment responses in severe sepsis.
Publication TypeJournal Article
Year of Publication2013
AuthorsMan M, Close SL, Shaw AD, Bernard GR, Douglas IS, Kaner RJ, Payen D, Vincent J-L, Fossceco S, Janes JM, Leishman AG, O'Brien L, Williams MD, Garcia JGN
JournalPharmacogenomics J
Volume13
Issue3
Pagination218-26
Date Published2013 Jun
ISSN Number1473-1150
KeywordsBiomarkers, 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
Abstract

<p>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.</p>

DOI10.1038/tpj.2012.1
Alternate JournalPharmacogenomics J.
PubMed ID22310353