Confirmatory GWAS Analysis of the Samples in the Marine Recruit Archive
Abstract
This study will validate novel NIHL susceptibility markers previously identified in a previous discovery phase Genome wide Association Study (GWAS) of Marine recruits. The objective of this project will confirm the results found in that pilot study (Award #: N00014-11-1-0523) in which saliva from a small number of subjects in the palcebo arm were identified to have nucleolin as a key dis-regulated protein leading to increased apoptosis in cochlear hair cells undergoing oxidative stress. The other 58 newly discovered SNPs found in the original NIHL Gene Chip study would be investigated with an anticipated 20-30% increase in statistical significance, thus increasing the known candidate NIHL-related SNPs in the literature by about 66%. In addition, this proposed GWAS will identify SNPs associated with N-Acetylcysteine (NAC) which has been reported to be efficacious as a treatment against noise induced hearing loss (NIHL) in Marine Recruits who received NAC during basic training. Results of that study were inconclusive because genetic factors were not taken into consideration to correlate with NAC efficacy. In this study, we would conduct NIHL susceptibility tests and then compare audiograms of high and low responders with genotyped saliva samples from the NAC arm of that Marine Recruit Study. The results would: 1) identify those SNPs as validated predictor of NIHL susceptibility and 2) identify those SNPs unique to metabolites of oxidative stress and those polymorphisms associated with NAC efficacy. Results of this study would predict subjects at risk of hearing loss and reveal antioxidant-dependant pathways affected by NAC, that will have an effect to protect subjects from NIHL. Results on the genetic factors will also be used to sort out the data from the Marine Recruit Study that shows a trend for NAC treatment, but did not achieve significance. The transitional nature of this research would give much needed information on NIHL susceptibility in a population of young healthy males.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 12, 2016
- Source ID
- N000141512518
Entities
People
- Rick A. Rogers
Organizations
- Office of Naval Research
- President and Fellows of Harvard College
- United States Navy