The causal effects of thyroid function and lipids on cholelithiasis: A Mendelian randomization analysis

Area of Science:

• Endocrinology
• Metabolic Diseases
• Genetics

Background:

• Thyroid dysfunction is increasingly recognized for its potential systemic effects.
• Lipid metabolism plays a crucial role in various physiological processes.
• Cholelithiasis (gallstones) represents a significant public health concern with complex etiology.

Purpose of the Study:

• To investigate the causal relationship between thyroid function and cholelithiasis.
• To determine if lipid metabolism traits mediate the association between thyroid function and gallstone formation.

Main Methods:

• A two-sample Mendelian randomization (MR) study design was employed.
• Multiple MR methods, including IVW, weighted median, and MR-PRESSO, were utilized for robust estimation.
• Genetic variants associated with thyroid function and lipid traits served as instrumental variables.

Main Results:

• Elevated FT4 levels were causally associated with an increased risk of cholelithiasis.
• Low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B were independently associated with higher gallstone risk.
• LDL-C and apolipoprotein B significantly mediated the causal effect of FT4 on cholelithiasis, accounting for 17.4% and 13.5% of the effect, respectively.

Conclusions:

• FT4, LDL-C, and apolipoprotein B exhibit significant causal effects on cholelithiasis risk.
• Lipid traits, specifically LDL-C and apolipoprotein B, mediate the impact of thyroid function on gallstone development.
• Individuals with elevated FT4 levels warrant close monitoring for gallstone risk due to the mediating role of lipids.