Experimental and Clinical Studies of Presbyacusis

The Medical University of South Carolina (MUSC) Longitudinal Cohort Study of Age-related Hearing Loss is an ongoing (1988-current) community-based cohort study in Charleston, South Carolina, USA. The purpose of this study is to determine the audiological features of age-related hearing loss, identify genes and variants that cause or contribute to age-related hearing loss, a common and complex disease with a strong genetic component, and provide scientific bases for diagnosis, rehabilitation, and prevention. Participants are continuously enrolled and are recruited through community events, online and print advertisements, and participant referral. Recruitment, consenting, and study protocols are approved by the Institutional Review Board for Human Research at MUSC. Two to six visits are scheduled to complete a baseline examination that include, but are not limited to, pure-tone thresholds at conventional and extended high frequencies, middle-ear measures, speech recognition in quiet and noise, otoacoustic emissions, auditory brainstem responses, a battery of cognitive measures, and responses to self-report questionnaires including demographics, medical history, medications, hearing difficulties, hearing and hearing-aid history, and noise exposure history. Blood samples are obtained for clinical chemistries and DNA extraction for whole exome sequencing (WXS). Following completion of the baseline protocol, participants return annually to obtain an updated audiogram, health history, and hearing health history. Every 2 to 3 years after baseline, participants attend a comprehensive follow-up visit where most of the baseline measures are repeated. In 2026, the participant sample included 1,800 adults of 18 to >80 years of age at enrollment (mean age ~ 60 years) with longitudinal data spanning up to ~ 33 years (~ 57% female; ~ 17% Black). Exome sequencing is carried out using the Agilent SureSelect X2 Target Enrichment System (version 5) and the Agilent SureSelect Human All Exon V5 kit, which included 5' and 3' UTRs. DNA was sheared using the Covaris S220 focused ultrasonicator. Libraries were sequenced on the Illumina HiSeq 2500. Variant loads per gene are calculated and compared between groups with normal hearing and hearing loss. Individual variants affecting pure-tone thresholds are also identified. “Hearing phenotype”, based on audiometric results, is determined only for participants with genomic data. These participants are classified into one of the following five hearing phenotypes, Older-Normal, Metabolic, Sensory, Unclassified, and Unselected (see PMID: 30180840, PMID: 38011198). Analyses are also conducted in a second, independent cohort from a clinical sample. ]]>
Inclusion criteria were 18 years or older and good general health to be able to attend multiple laboratory visits. Exclusion criteria were conductive hearing loss, active or history of otologic or neurologic disease or surgery, recent sudden sensorineural hearing loss, frequent fluctuations in hearing, inability to complete testing reliably, and inability to provide informed consent. ]]>