Abstract

Survivors of traumatic injuries confront many difficulties in their struggle to recover. Rehabilitation efforts are undercut by many complications. While traumatic injuries are the leading cause of death for Americans under the age of 44, they also are a significant reason for rehabilitation services. A critical interruption of the recovery process after traumatic injury is the development of Adult Respiratory Distress Syndrome (ARDS) or Acute Lung Injury (ALl). The goal of this study is to identify genetic polymorphisms that predict risk of ARDS or ALl following trauma. In this study, we will focus on candidate genes for pulmonary function including those involved in nitric oxide production, vascular resistance, cellular responses to injury, cellular signaling, and alveolar function. We will fist determine whether individual polymorphisms predict risk of ARDS or All following trauma (Aim 1). We will then determine whether the relationships between individual polymorphisms and ARDS/ALI following trauma are dependent on environmental factors (Aim 2). Using a hierarchical systems approach, we will then determine whether the relationships between individual polymorphisms and ARDS/ALI following trauma are dependent on one or more other polymorphisms (Aim 3). Finally, we will use a hierarchical systems approach to determine whether the relationships between combinations of polymorphisms and ARDS/ALI following trauma are dependent on one or more environmental factors (Aim 4). This study will capitalize on local expertise and resources in trauma medicine, biochemical and molecular genetics, statistical genetics, and bioinformatics to provide a comprehensive approach to the identification of genetic predictors of trauma recovery and rehabilitation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD047447-05
Application #
7541423
Study Section
Special Emphasis Panel (ZHD1-DSR-R (25))
Program Officer
Nitkin, Ralph M
Project Start
2004-12-15
Project End
2010-11-30
Budget Start
2008-12-01
Budget End
2010-11-30
Support Year
5
Fiscal Year
2009
Total Cost
$350,780
Indirect Cost

  Institution

Name
Dartmouth College
Department
Genetics
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755

  Publications

Greene, Casey S; Himmelstein, Daniel S; Kiralis, Jeff et al. (2010) The Informative Extremes: Using Both Nearest and Farthest Individuals Can Improve Relief Algorithms in the Domain of Human Genetics. Lect Notes Comput Sci 6023:182-193
Greene, Casey S; Sinnott-Armstrong, Nicholas A; Himmelstein, Daniel S et al. (2010) Multifactor dimensionality reduction for graphics processing units enables genome-wide testing of epistasis in sporadic ALS. Bioinformatics 26:694-5
Greene, Casey S; Himmelstein, Daniel S; Moore, Jason H (2010) A Model Free Method to Generate Human Genetics Datasets with Complex Gene-Disease Relationships. Lect Notes Comput Sci 6023:74-85
Greene, Casey S; Himmelstein, Daniel S; Nelson, Heather H et al. (2010) Enabling personal genomics with an explicit test of epistasis. Pac Symp Biocomput :327-36
Morris Jr, John A; Francois, Cedric; Olson, Paul K et al. (2009) Genetic variation in complement component 2 of the classical complement pathway is associated with increased mortality and infection: a study of 627 patients with trauma. J Trauma 66:1265-70; discussion 1270-2
Norris, Patrick R; Canter, Jeffrey A; Jenkins, Judith M et al. (2009) Personalized medicine: genetic variation and loss of physiologic complexity are associated with mortality in 644 trauma patients. Ann Surg 250:524-30
Moore, Jason H; Williams, Scott M (2009) Epistasis and its implications for personal genetics. Am J Hum Genet 85:309-20
Pattin, Kristine A; Moore, Jason H (2009) Role for protein-protein interaction databases in human genetics. Expert Rev Proteomics 6:647-59
Sloan, Chantel D; Andrew, Angeline D; Duell, Eric J et al. (2009) Genetic population structure analysis in New Hampshire reveals Eastern European ancestry. PLoS One 4:e6928
Greene, Casey S; Penrod, Nadia M; Williams, Scott M et al. (2009) Failure to replicate a genetic association may provide important clues about genetic architecture. PLoS ONE 4:e5639

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