Improving Understanding of the Biological Basis of Tinnitus: A Multi-Omics Approach in Two Large Cohorts of Women
Royal National Institute for Deaf People
Brigham and Women's Hospital
There is a critical need to improve understanding of the biological basis of tinnitus, unravel the diverse etiologies that underlie this heterogeneous condition, and advance development of tailored treatments based on a precision medicine data-driven approach. Accumulating evidence suggests complex interactions between genetic, demographic, lifestyle and other environmental factors influence the generation of tinnitus. Our objectives are to identify a metabolomic signature of tinnitus and to use a multi-omics approach to bridge tinnitus-related metabolomic data with genomic data and data on a wide array of individual, lifestyle and environmental factors. We will interrogate metabolite profiles using targeted and untargeted discovery approaches to develop objective tinnitus biomarkers and advance understanding of tinnitus pathogenesis. We will leverage the extensive longitudinal data collected in 2 large U.S. cohorts with long follow-up, the Nurses’ Health Studies I and II, to conduct network analyses that integrate these data with our wealth of hearing-related and non-audiological phenotypic data to study the biological basis of tinnitus. We will include all participants with tinnitus and existing metabolomics data (n=4,855), adding additional participants as data accrue. We aim to: (1) identify a set of metabolites that can act as a biomarker of tinnitus (“metabolomic signature”), (2) identify plasma metabolites associated with risk of incident tinnitus, and (3) employ a network approach to interrogate tinnitus genotype-metabolomic-phenotype relationships. Our multidisciplinary approach could elucidate pathogenic changes that lead to tinnitus, provide insight into the classification of subtypes of this heterogeneous disorder, identify potential treatment targets, and inform the development of personalized therapeutics.
2.1 Biological and endogenous factors