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

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. ((C) 2022 Elsevier Inc. All rights reserved.)

Automated summary

This study conducted a Mendelian randomization analysis to investigate the association between genetic variants related to thyroid function and the risk of age-related macular degeneration (AMD). The results showed that higher levels of free thyroxine (FT4) were associated with an increased risk of AMD, while higher levels of thyroid-stimulating hormone (TSH) were associated with a decreased risk of AMD.