A Two-Way Mendelian Randomization Analysis on the Link between Thyroid Activity Function and Coronary Atherosclerosis

Area of Science:

• Cardiovascular Research
• Endocrinology
• Genetics

Background:

• Coronary artery disease (CAD) is primarily caused by coronary atherosclerosis.
• Thyroid hormones are potential risk factors beyond standard modifiable cardiovascular risk factors (SMuRFs).

Purpose of the Study:

• To investigate the causal relationship between thyroid function and coronary atherosclerosis.
• To identify thyroid-related risks for coronary artery disease.

Main Methods:

• Utilized Mendelian Randomization (MR) analysis with large-scale genetic data from IEU OpenGWAS, Finngen R9, and ThyroidOmics Consortium.
• Analyzed single nucleotide polymorphisms (SNPs) associated with hypothyroidism, Graves' disease, other hyperthyroidism, TSH, FT4, and coronary atherosclerosis.
• Employed inverse variance weighting (IVW), weighted median (WM), and MR-Egger methods, with sensitivity analyses including Cochran's Q test and leave-one-out analysis.

Main Results:

• Genetic predisposition to hypothyroidism, Graves' disease, and other hyperthyroidism significantly increases the likelihood of coronary atherosclerosis.
• No causal link was found between free thyroxine (FT4) or thyroid-stimulating hormone (TSH) levels and coronary atherosclerosis.
• Reverse MR analysis showed no association between coronary atherosclerosis and thyroid function phenotypes.

Conclusions:

• Thyroid dysfunction, specifically hypothyroidism and hyperthyroidism, is causally linked to coronary atherosclerosis.
• Findings contribute to understanding cardiovascular risk factors for CAD.
• Highlights the importance of considering thyroid health in managing coronary artery disease.