Genetically elevated FT4 levels tied to higher age-related macular degeneration risk

Patients who have genetically elevated free thyroxine (FT4) levels are at heightened risk of age-related macular degeneration (AMD), according to the results of a Mendelian randomization (MR) study.

Researchers identified single-nucleotide polymorphisms associated with FT4 and thyroid stimulating hormone (TSH) from a genome-wide association study (GWAS) of 72,167 individuals of European descent. They also summarized data for AMD from a GWAS published by International Age-related Macular Degeneration Genomics Consortium involving 33,526 individuals (16,144 patients and 17,832 controls).

Using the inverse-variance-weighted method, MR analysis revealed that each one-standard deviation (SD) increase in genetically predicted FT4 levels was associated with an 18.9-percent increase in the risk of overall AMD (p=0.005).

In an analysis that controlled for TSH level, the causal link between elevated FT4 levels and the risk of AMD persisted (odds ratio [OR], 1.207; p=0.004). Of note, there was a nominal 10 percent decrease in the overall AMD risk per one SD increase in TSH levels (p=0.032).

However, when multivariable MR analysis was adjusted for FT4 level, there was no direct causal relationship observed between TSH level and AMD risk (95 percent confidence interval, 0.810–1.125; p=0.582).

More studies are needed to elucidate the mechanism underlying the causal relationship between FT4 levels and AMD risk.