Causal Associations of Thyroid Function and Age-Related Macular Degeneration: A Two-Sample Mendelian Randomization Study

Xi Li; Hanyu Li; Jingdan Cheng; Mengting Wang; Yiming Zhong; Guilian Shi; A-Yong Yu

doi:10.1016/j.ajo.2022.01.026

Causal Associations of Thyroid Function and Age-Related Macular Degeneration: A Two-Sample Mendelian Randomization Study

Am J Ophthalmol. 2022 Jul:239:108-114. doi: 10.1016/j.ajo.2022.01.026. Epub 2022 Feb 14.

Authors

Xi Li¹, Hanyu Li², Jingdan Cheng³, Mengting Wang¹, Yiming Zhong¹, Guilian Shi⁴, A-Yong Yu⁵

Affiliations

¹ From the Eye Hospital and School of Ophthalmology and Optometry (X.L., M.W., Y.Z., G.S.A-Y.Y), Wenzhou Medical University, Wenzhou, Zhejiang, China; National Clinical Research Center for Ocular Disease (X.L., M.W., Y.Z., G.S.A-Y.Y), Wenzhou, Zhejiang, China.
² Department of Ggeriatric Mmedicine of the First Affiliated Hospital (H.L.), School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
³ Department of Neurology (J.C.), Shanxi Cardiovascular Hospital, Taiyuan 030000, Shanxi Province, China.
⁴ From the Eye Hospital and School of Ophthalmology and Optometry (X.L., M.W., Y.Z., G.S.A-Y.Y), Wenzhou Medical University, Wenzhou, Zhejiang, China.
⁵ From the Eye Hospital and School of Ophthalmology and Optometry (X.L., M.W., Y.Z., G.S.A-Y.Y), Wenzhou Medical University, Wenzhou, Zhejiang, China; National Clinical Research Center for Ocular Disease (X.L., M.W., Y.Z., G.S.A-Y.Y), Wenzhou, Zhejiang, China. Electronic address: yaybetter@hotmail.com.

PMID: 35176254
DOI: 10.1016/j.ajo.2022.01.026

Abstract

Purpose: To determine whether causal association lies between thyroid function and age-related macular degeneration (AMD) risk in human beings.

Design: Two-sample Mendelian randomization (MR) study.

Methods: The single-nucleotide polymorphisms associated with free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were selected from a genome-wide association study (GWAS) of 72,167 individuals of European descent. Summary-level data for AMD were obtained from a GWAS published by the International Age-related Macular Degeneration Genomics Consortium of 33,526 individuals (16,144 cases and 17,832 controls). An inverse-variance-weighted (IVW) method was the main MR analysis. Maximum likelihood, weighted median, MR-Egger, MR-pleiotropy residual sum outlier methods were used for the sensitivity analysis.

Results: An increase of 1 SD in genetically predicted FT4 levels was found to be significantly associated with an 18.9 % increase in the overall AMD risk (P = .005). In the multivariable MR analysis controlling for TSH level, the causal effect of FT4 level on the risk of AMD remained (odds ratio [OR] = 1.207, P = .004). A 1-SD increase in TSH levels was nominally associated with a 10.0% decrease in the overall AMD risk (P = .032). After adjusting for FT4 level by multivariable MR analysis, no direct causal relationship was found between TSH level and AMD risk (95% CI = 0.810, 1.125, P = .582).

Conclusions: Genetic variants predisposing to higher FT4 levels within the normal range were associated with higher AMD risk. Further studies are required to understand the mechanism underlying this putative causal relationship.

Keywords: Age-related macular degeneration; Mendelian randomization; thyroid function.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Genome-Wide Association Study
Humans
Macular Degeneration* / genetics
Mendelian Randomization Analysis* / methods
Polymorphism, Single Nucleotide
Risk Factors
Thyroid Gland
Thyrotropin / genetics

Substances

Thyrotropin