Association Between Thyroid-Stimulating Hormone and Renal Function: a Mendelian Randomization Study

Area of Science:

• Endocrinology
• Nephrology
• Genetic Epidemiology

Background:

• Observational studies suggest a link between thyroid-stimulating hormone (TSH) and estimated glomerular filtration rate (eGFR).
• Causality remains unclear due to potential confounding and reverse causation in traditional epidemiological studies.

Purpose of the Study:

• To investigate the causal relationship between TSH and eGFR using a Mendelian randomization (MR) approach.
• To determine if genetically influenced TSH levels affect kidney function.

Main Methods:

• A Mendelian randomization analysis was performed on 10,603 participants from the SPECT-China study.
• Weighted genetic risk scores (GRS) for TSH were constructed using TSH-related single nucleotide polymorphisms.
• Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula; instrumental variables (IV) were employed.

Main Results:

• Multivariable analysis showed higher measured TSH associated with lower eGFR (B -0.717).
• MR analysis revealed TSH_GRS significantly associated with TSH but not with eGFR (B -0.127).
• No causal associations between genetically instrumented TSH and eGFR were observed.

Conclusions:

• Mendelian randomization analysis suggests no causal association between TSH and eGFR.
• Genetically elevated TSH concentrations do not appear to influence renal function.
• This genetic approach mitigates confounding and reverse causation inherent in observational studies.