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  • Thyroid Function and AMD Risk

    By Lynda Seminara
    Selected by Richard K. Parrish II, MD
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    Journal Highlights

    American Journal of Ophthalmology, July 2022

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    Although a link between thyroid hor­mones and risk of age-related macular degeneration (AMD) has been reported for animal models, findings of subse­quent observational studies have been inconsistent, suggesting that hidden confounding factors could affect results. To eliminate potential confounders, Li et al. explored the relationship between thyroid hormone function and AMD using Mendelian randomization (MR). They found that genetic variants predisposing patients to free thyroxine (FT4) levels in the high-normal range were associated with greater AMD dis­ease risk. However, there was no clear evidence of an independent causal relationship between AMD and levels of thyroid-stimulating hormone (TSH).

    To enhance their study’s statistical power, the authors used two separate population samples. In one, the single-nucleotide polymorphisms associated with FT4 and TSH were extracted from a genome-wide association study (GWAS) of 72,167 people of European descent. In the other, summary-level data for AMD were obtained from an International Age-Related Macular Degeneration Genomics Consortium GWAS that included 16,144 patients with AMD and 17,832 control subjects, recruited from 26 studies.

    The results showed that each standard deviation (SD) increase in genetically predicted FT4 levels was significantly associated with an 18.9% increase in overall AMD risk (p = .005). In the multivariable MR analysis that was controlled for TSH level, the causal effect of FT4 level on the risk of AMD also was strong (odds ratio, 1.207; p = .004). In contrast, a 1-SD increase in TSH levels coincided just nominally with a 10% reduction in overall AMD risk (p = .032). Subsequent multivari­able MR analysis adjusted for FT4 level did not show a direct causal relation­ship between TSH level and AMD risk (p = .582).

    Given the multiple sensitivity analy­ses for pleiotropic genes plus adequate statistical power to detect causal associ­ations, the overall findings of this study suggest an intrinsic negative effect of thyroid hormone function on the development of AMD. The authors encourage investigation of the mecha­nism behind the apparent link between FT4 and AMD risk, which may be a basis for new risk-reduction strategies.

    The original article can be found here.