Document Detail


Pathway genetic load allows simultaneous evaluation of multiple genetic associations.
MedLine Citation:
PMID:  20381257     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
OBJECTIVE: Despite the general success of genome-wide association studies, much heritability remains unidentified in many disease states. Some of this 'missing' heritability may lie in epistatic interactions among multiple loci, which are typically ignored. We utilized a method for simultaneous evaluation of epistatic interactions between allelic variations within genes confined to a single pathway, which we have termed as pathway genetic load (PGL).
METHODS: In separate analyses, we evaluated the risk for sepsis and for death associated with alleles at six loci in the TLR4 signaling and response pathway previously known or suspected to be linked to the development of sepsis after traumatic injury. We evaluated 155 patients with > or =15% TBSA burns and without significant non-burn trauma [ISS < or =16], traumatic or anoxic brain injury or spinal cord injury, who survived > 48 h post-admission. Clinical data were collected prospectively and candidate genotypes were determined by TaqMan assay.
RESULTS: After adjustment for burn size, inhalation injury, age, gender and race, PGL was associated with increased probability for complicated sepsis (aOR=1.59; 95%CI=1.11-2.29; p=0.011) and death (aOR=1.75; 95%CI=1.11-2.76; p=0.017).
CONCLUSION: Relative size and variability of aORs indicate greater power to detect genetic associations with PGL compared to the analysis of loci individually by multivariate logistic regression.
Authors:
Ryan M Huebinger; Harold R Garner; Robert C Barber
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-04-08
Journal Detail:
Title:  Burns : journal of the International Society for Burn Injuries     Volume:  36     ISSN:  1879-1409     ISO Abbreviation:  Burns     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-07-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8913178     Medline TA:  Burns     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  787-92     Citation Subset:  IM    
Copyright Information:
2010 Elsevier Ltd and ISBI. All rights reserved.
Affiliation:
Department of Surgery, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
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MeSH Terms
Descriptor/Qualifier:
Grant Support
ID/Acronym/Agency:
5P50GM21681-43/GM/NIGMS NIH HHS; 5T32GM008593-13/GM/NIGMS NIH HHS

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