Causal linkage of Graves’ disease with aging: Mendelian randomization analysis of telomere length and age-related phenotypes

Abstract

Abstract Background Aging is an irreversible progressive decline in physical function. Graves’ disease (GD) is a common cause of hyperthyroidism and is characterized by elevated levels of the thyroid hormone (TH). High TH levels are associated with aging and a shortened lifespan. The causal relationship between GD and aging has yet to be investigated. Methods We used genome-wide association study (GWAS) datasets and Mendelian randomization (MR) analysis to explore the causal link between GD and aging. To assess the statistical power of instrumental variables (IVs), F-statistics and R 2 were used. MR analysis was conducted using inverse-variance weighting (IVW), MR-Egger, weighted median, and weighted mode. The odds ratio (OR) and 95% CI were calculated to estimate the relative risk of GD to the outcomes. The Cochran Q test, I 2, MR-PRESSO test, and MR-Egger regression intercept were calculated using statistical and leave-one-out analyses to test the heterogeneity, horizontal pleiotropy, and stability of the IVs on the outcomes. Results F-statistics of the five IVs were greater than 10, and the R 2 values ranged from 0.033 to 0.156 (R 2 > 0.01). According to the results of the IVW analysis, GD had no causal effect on facial aging (p = 0.189), age-related macular degeneration (p = 0.346), and Alzheimer’s disease (p = 0.479). There was a causal effect of GD on the remaining outcomes: telomere length (TL) (OR = 0.982; 95%CI:0.969–0.994; p = 0.004), senile cataract (OR = 1.031; 95%CI:1.002–1.060; p = 0.033), age-related hearing impairment (OR = 1.009; 95%CI:1.004–1.014; p = 0.001), chronic obstructive pulmonary disease (COPD) (OR = 1.055; 95%CI:1.008–1.103; p = 0.020), and sarcopenia (OR = 1.027; 95%CI:1.009–1.046; p = 0.004). Conclusions GD accelerates the occurrence of age-related phenotypes including TL, senile cataracts, age-related hearing impairment, COPD, and sarcopenia. In contrast, there are no causal linkages between GD and facial aging, age-related macular degeneration, or Alzheimer’s disease. Further experimental studies could be conducted to elucidate the mechanisms by which GD facilitates aging, which could help slow down the progress of aging.

Keywords

• Mendelian randomization
• Graves’ disease
• Aging
• Age-related phenotype
• Single nucleotide polymorphism