Beyond single-marker analyses

Mining whole genome scans for insights into treatment responses in severe sepsis

M. Man, S. L. Close, A. D. Shaw, G. R. Bernard, I. S. Douglas, R. J. Kaner, D. Payen, J. L. Vincent, S. Fossceco, J. M. Janes, A. G. Leishman, L. O'Brien, M. D. Williams, Joe GN Garcia

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)218-226
Number of pages9
JournalPharmacogenomics Journal
Volume13
Issue number3
DOIs
StatePublished - Jun 2013
Externally publishedYes

Fingerprint

Sepsis
Biomarkers
Genome
Genome-Wide Association Study
Genetic Markers
Genes
Disease Progression
Therapeutics
Randomized Controlled Trials
Morbidity
Mortality

Keywords

  • Drotrecogin alfa (activated)
  • epistasis
  • genetic markers
  • genome-wide association study
  • polymorphism
  • severe sepsis

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics

Cite this

Beyond single-marker analyses : Mining whole genome scans for insights into treatment responses in severe sepsis. / Man, M.; Close, S. L.; Shaw, A. D.; Bernard, G. R.; Douglas, I. S.; Kaner, R. J.; Payen, D.; Vincent, J. L.; Fossceco, S.; Janes, J. M.; Leishman, A. G.; O'Brien, L.; Williams, M. D.; Garcia, Joe GN.

In: Pharmacogenomics Journal, Vol. 13, No. 3, 06.2013, p. 218-226.

Research output: Contribution to journalArticle

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, JGN 2013, 'Beyond single-marker analyses: Mining whole genome scans for insights into treatment responses in severe sepsis', Pharmacogenomics Journal, vol. 13, no. 3, pp. 218-226. https://doi.org/10.1038/tpj.2012.1
Man, M. ; Close, S. L. ; Shaw, A. D. ; Bernard, G. R. ; Douglas, I. S. ; Kaner, R. J. ; Payen, D. ; Vincent, J. L. ; Fossceco, S. ; Janes, J. M. ; Leishman, A. G. ; O'Brien, L. ; Williams, M. D. ; Garcia, Joe GN. / Beyond single-marker analyses : Mining whole genome scans for insights into treatment responses in severe sepsis. In: Pharmacogenomics Journal. 2013 ; Vol. 13, No. 3. pp. 218-226.
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