Causal associations of thyroid function and sudden sensorineural hearing loss: a bidirectional and multivariable Mendelian randomization study

Jialei Chen; Chao Wu; Jing He; Linsui Wu; Yongkang Yang; Shixun Zhong; Jing Luo

doi:10.3389/fneur.2023.1269545

Causal associations of thyroid function and sudden sensorineural hearing loss: a bidirectional and multivariable Mendelian randomization study

Front Neurol. 2023 Nov 27:14:1269545. doi: 10.3389/fneur.2023.1269545. eCollection 2023.

Authors

Jialei Chen^{1

2

3}, Chao Wu⁴, Jing He¹, Linsui Wu¹, Yongkang Yang⁵, Shixun Zhong¹, Jing Luo^{6

7}

Affiliations

¹ Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
² Department of Pathology and Pathophysiology, Chongqing Medical University, Chongqing, China.
³ Molecular Medicine and Cancer Research Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.
⁴ Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
⁵ Department of Clinical Medicine, Clinical Medical College of Chengdu University, Chengdu, China.
⁶ Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
⁷ Department of Pathology, Chongqing Medical University, Chongqing, China.

Abstract

Background: Observational studies have indicated a potential association between thyroid dysfunction and the risk of sudden sensorineural hearing loss (SSNHL). However, the precise causal relationship between the two remains uncertain. The objective of our study was to assess the causal influence of thyroid function on SSNHL by employing a bidirectional and multivariable Mendelian randomization (MR) approach.

Methods: Single-nucleotide polymorphisms (SNPs) associated with free thyroid (FT4) and thyroid stimulating hormone (TSH) were selected from the summary data of a large genome-wide association study (GWAS) conducted on European individuals. The summary-level data of SSNHL were also obtained from a GWAS, which included 196,592 participants (1,491 cases and 195,101 controls). The MR analysis primarily utilized the inverse variance weighted (IVW) method, with sensitivity analyses performed using the weighted median, MR-Egger, and MR-PRESSO approaches.

Results: In the IVW method, an elevated genetically predicted FT4 level was found to effectively reduce the risk of SSNHL (OR = 0.747, 95% CI = 0.565-0.987, P = 0.04). These findings were consistent when conducting multivariate MR analysis, which adjusted for TSH levels (OR = 0.929, 95% CI = 0.867-0.995, P = 0.036). However, genetically predicted TSH levels did not emerge as a risk factor for SSNHL (OR = 1.409, 95% CI = 0.895-1.230, P = 0.547). Furthermore, even after adjusting for FT4 levels in the multivariate MR analysis, no evidence of a direct causal relationship between TSH levels and the risk of SSNHL was observed (OR = 1.011, 95% CI = 0.880-1.161, P = 0.867). The reverse MR analysis showed that there was no evidence of a direct causal relationship between SSNHL and the risk of FT4 level (OR = 1.026, 95% CI = 0.999-1.054, P = 0.056) or TSH level (OR = 1.002, 95% CI = 0.989-1.015, P = 0.702).

Conclusion: Within the normal range, genetic variants associated with higher FT4 levels demonstrate a potential protective effect against SSNHL, whereas there is no direct causal relationship between TSH levels and the risk of SSNHL.

Keywords: Mendelian randomization; free thyroxine; risk factor; sudden sensorineural hearing loss; thyroid-stimulating 2 hormone.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Natural Science Foundation of Chongqing of China (cstc2019jcyj-msxm0842) and the Key Project of Technical Innovation, Application and Development in Health Field of Chongqing (CSTC2021jscx-gksb-N0012).