Association of Thyroid-Stimulating Hormone With All-Cause Mortality: A 2-Sample Mendelian Randomization Study

Area of Science:

• Endocrinology
• Genetics
• Epidemiology

Background:

• Thyroid-stimulating hormone (TSH) is a key indicator of thyroid function and is linked to various health outcomes, including mortality.
• The causal relationship between TSH levels and mortality risk has remained unclear.

Purpose of the Study:

• To investigate the potential causal association between TSH levels and all-cause mortality.
• Utilize Mendelian randomization (MR) analyses for robust causal inference.

Main Methods:

• Employed MR analyses with single-nucleotide polymorphisms (SNPs) associated with TSH levels as genetic instruments.
• Utilized mortality data from the UK Biobank (384,344 participants) and Cox proportional hazards regression.
• Calculated TSH genetic risk score (GRS) to assess associations with all-cause and cause-specific mortality.

Main Results:

• A 1-unit increase in TSH was associated with a decreased risk of all-cause mortality (OR 0.972).
• This association was largely driven by a reduced risk of respiratory disease mortality (OR 0.881).
• Higher TSH GRS categories showed a significant trend towards lower all-cause mortality (P for trend < .01).

Conclusions:

• Elevated TSH levels are causally associated with a lower risk of all-cause mortality.
• The protective effect of higher TSH levels on mortality is significantly influenced by reduced respiratory disease mortality.