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Published on: July 14, 2016
Causal Associations of Thyroid Function and Age-Related Macular Degeneration: A Two-Sample Mendelian Randomization
Xi Li1, Hanyu Li2, Jingdan Cheng3
1From 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.
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.
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