The roles of modifiable risk factor and immunoglobulin G N-glycome in the risk of hearing loss

Author Identifier

Yulu Zheng

https://orcid.org/0000-0002-9639-8863

Date of Award

2023

Document Type

Thesis - ECU Access Only

Publisher

Edith Cowan University

Degree Name

Doctor of Philosophy

School

School of Medical and Health Sciences

First Supervisor

Wei Wang

Abstract

Background

Hearing loss is one of the leading causes of years lived with disability and the most prevalent sensory impairments impairment affecting people of all ages, which generates a substantial burden on the adult population.

Aims

Study I. To explore population attributable fractions (PAFs) of modifiable risk factors on hearing loss within a cross-sectional design.

Study II. To screen whether the IgG N-glycome composition is associated with the risk of age-related hearing loss mediated by age in a cross-sectional study.

Study III. To investigate genetic evidence for putative causal relationships between modifiable risk factors and sensorineural hearing loss.

Methods

Study I. A cross-sectional study within Busselton Healthy Ageing Study (BHAS) was conducted from May 2010 to December 2015. Pure-tone audiometry was used to measure the hearing status. 4,897 participants were included in the analyses. Modified Poisson regression and PAF were the primary methods to evaluate associations between modifiable risk factors and hearing loss.

Study II. The IgG N-glycan analyses were conducted based on the BHAS, with 700 middle-aged and 695 older adults. Modified Poisson regression was used to assess the association between IgG N-glycome composition and hearing loss.

Study III. In the two-sample mendelian randomization (MR) framework, both univariable and multivariable MR analyses were used to examine the potential causal roles of major modifiable risk factors on the risk of hearing loss by using the summary-level statistics obtained from the established genome-wide association studies.

Results

Study I. Of 4,897 participants, the mean (SD) age was 57.9 (5.8) years; 2224 were men (45.4%). Over 50% of hearing loss cases were attributed to modifiable risk factors, in which behavioural factors were the predominant risk factors for hearing loss (PAF: 23.7%), with low protection of hearing being the largest (PAF: 21.9%).

Study II. In middle-aged adults, we found associations of hearing loss with high levels of agalactosylated IgG N-glycans (prevalence ratio [PR] 1.25, 95% CI, 1.04-1.51) and asialylated N-glycans (PR 1.26, 95% CI, 1.05-1.51), whereas low levels of monosialylated N-glycans (PR 0.79, 95% CI, 0.66-0.97) and N-glycans with high-mannose glycoforms (PR 0.81, 95% CI, 0.67-0.98), after adjusting for potential confounders.

Study III. The genetic evidence was observed for an independent causal effect of physical activity sensorineural hearing loss adjusting for cigarettes per day (inverse-variance weighted odds ratio [IVW OR] 0.57, 95% CI = 0.37, 0.86 per SD increase in moderate to vigorous physical activity level; IVW OR 0.63, 95% CI = 0.47, 0.83 per SD increase in the number of days/week of vigorous physical activity 10+ minutes) and an independent causal effect of triglycerides when controlling for high-density lipoprotein cholesterol (IVW OR 1.11, 95% CI = 1.04, 1.18 per SD increase in triglycerides).

Conclusions

Study I and Study III indicated that public health programs should highlight the importance of modifiable risk factors in the management of sensorineural hearing loss. Study II suggested that proinflammatory alterations of IgG N-glycome composition may play a key role in hearing loss or cochlear degeneration.

Access Note

Access to this thesis has been embargoed until 1st March 2027

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