A bidirectional Mendelian randomisation study to evaluate the relationship between body constitution and hearing loss

Area of Science:

• Genetics
• Epidemiology
• Audiology

Background:

• Hearing loss is linked to non-auditory health issues.
• The role of hearing function in noise-obesity associations is unclear.
• Mendelian randomization (MR) can explore causal links between body constitution and hearing impairments.

Purpose of the Study:

• Investigate causal relationships between body constitution (BMI, WC, BFP) and hearing impairments (sensorineural, noise-induced, age-related).
• Assess if hearing functions mediate noise-obesity associations.
• Explore bidirectional causal links using MR.

Main Methods:

• Utilized genome-wide association study summary statistics from European adults (N=210,088–360,564).
• Applied Mendelian randomization (MR) for forward and reverse analyses.
• Conducted colocalization analysis at the FTO locus for BMI and age-related hearing impairment (ARHI).
• Employed random effects inverse variance-weighted method and sensitivity analyses.

Main Results:

• Colocalization analysis indicated a shared causal variant at the FTO gene for BMI and ARHI.
• No robust evidence found for body constitution causally influencing hearing loss.
• ARHI showed a negative association with BMI and body fat percentage, suggesting ARHI may worsen body constitution.
• Hearing loss did not appear to mediate the association between noise exposure and body constitution.

Conclusions:

• The FTO gene may play a role in the association between BMI and ARHI.
• Evidence suggests age-related hearing impairment might negatively affect body constitution.
• Hearing function is unlikely to be a significant mediator in the noise-obesity relationship.