A two-sample bidirectional Mendelian randomization analysis between telomere length and hyperthyroidism.

Area of Science:

• Genetics
• Endocrinology
• Molecular Biology

Background:

• Hyperthyroidism, characterized by low thyrotropin, presents significant health risks including cardiac issues, osteoporosis, and increased mortality.
• The causal relationship between telomere length (TL) and hyperthyroidism has not been clearly established.

Purpose of the Study:

• To investigate the potential causal relationship between telomere length (TL) and hyperthyroidism using a bidirectional Mendelian randomization (MR) approach.

Main Methods:

• A two-sample bidirectional Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW), Weighted Median (WM), and MR Egger methods.
• Summary statistics for TL were obtained from UK Biobank (n=472,174), and for hyperthyroidism from GWAS Catalog (n=460,499) and FinnGen (n=173,938).
• 139 genome-wide significant single nucleotide polymorphisms (SNPs) were used as instrumental variables for TL.

Main Results:

• Forward MR analyses indicated a significant inverse causal effect of TL on hyperthyroidism; increased genetically predicted TL was associated with decreased hyperthyroidism risk (IVW from GWAS Catalog OR: 0.659, p<0.001; IVW from FinnGen OR: 0.634, p=0.001).
• Consistent results were observed across different MR methods, and reverse MR analysis showed no evidence of a causal effect of hyperthyroidism on TL.
• Sensitivity analyses confirmed the robustness of the findings, indicating minimal bias.

Conclusions:

• Longer telomere length is causally associated with a reduced risk of developing hyperthyroidism.
• These findings suggest potential therapeutic targets and highlight the importance of considering telomere dynamics in hyperthyroidism research.
• Further research is warranted to validate the impact of hyperthyroidism on telomere length.