DNA Methylation Patterns Associated with Tinnitus in Young Adults-A Pilot Study

Area of Science:

• Epigenetics
• Genomics
• Otolaryngology

Background:

• Tinnitus, the perception of sound without external stimuli, is a common hearing issue.
• Genetic, environmental, and lifestyle factors are implicated in tinnitus development.
• Epigenetic modifications like DNA methylation may play a role in tinnitus pathogenesis.

Purpose of the Study:

• To investigate DNA methylation patterns in saliva as a potential indicator of tinnitus.
• To identify differentially methylated regions (DMRs) associated with tinnitus in young adults.
• To explore the utility of saliva as a surrogate tissue for epigenetic studies in tinnitus.

Main Methods:

• Genome-wide DNA methylation analysis of over 850,000 CpG sites using the Infinium Human Methylation EPIC BeadChip.
• Comparison of saliva DNA methylation profiles between 24 young adults with chronic tinnitus and 24 age-, sex-, and ethnicity-matched controls.
• Application of the Bumphunter algorithm to identify statistically significant DMRs associated with tinnitus, using an FDR-adjusted p-value threshold of 0.05.

Main Results:

• Identified 25 differentially methylated regions (DMRs) associated with tinnitus.
• Discovered hypermethylated DMRs near genes including LCLAT1, RUNX1, and RUFY1.
• Found hypomethylated DMRs near genes such as HLA-DPB2, PM20D1, and MUC4, with some associations potentially explained by genetic variation.

Conclusions:

• Epigenetic alterations, identified via DNA methylation in saliva, are linked to tinnitus.
• Genes near DMRs are involved in auditory function, cardiovascular disease, psychiatric conditions, and immune and metabolic disorders, aligning with known tinnitus comorbidities.
• Saliva serves as a viable surrogate tissue for studying the epigenetic underpinnings of tinnitus, warranting larger-scale validation studies.