Causal associations of thyroid function and sudden sensorineural hearing loss: a bidirectional and multivariable...

Area of Science:

• Genetics
• Endocrinology
• Otolaryngology

Background:

• Observational studies suggest a link between thyroid dysfunction and sudden sensorineural hearing loss (SSNHL).
• The exact causal relationship between thyroid function and SSNHL remains unclear.
• Mendelian randomization (MR) can help elucidate causal links.

Purpose of the Study:

• To investigate the causal effect of thyroid function on SSNHL risk.
• To employ a bidirectional and multivariable Mendelian randomization (MR) approach.

Main Methods:

• Selected single-nucleotide polymorphisms (SNPs) for free thyroid (FT4) and thyroid stimulating hormone (TSH) from large genome-wide association studies (GWAS) in European individuals.
• Utilized summary-level data for SSNHL from a GWAS of 196,592 participants.
• Applied the inverse variance weighted (IVW) method with sensitivity analyses (weighted median, MR-Egger, MR-PRESSO).

Main Results:

• Elevated genetically predicted FT4 levels were associated with reduced SSNHL risk (IVW: OR=0.747, P=0.04).
• Multivariable MR adjusting for TSH confirmed FT4's protective effect (OR=0.929, P=0.036).
• Genetically predicted TSH levels showed no causal association with SSNHL risk in either direction.

Conclusions:

• Genetic variants linked to higher FT4 levels may offer protection against SSNHL within the normal range.
• No direct causal relationship was found between TSH levels and SSNHL risk.