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Genetic study indicates that higher free thyroxine (fT4) levels are causally linked to lower metabolic syndrome (MetS) risk, with fT4 positively associated with high-density lipoprotein cholesterol (HDL-C) and thyroid-stimulating hormone (TSH) linked to triglycerides (TG). The research suggests a possible causal effect of HDL-C on reference-range TSH levels.

The following is a summary of “Thyroid Function and Metabolic Syndrome: A Two-Sample Bidirectional Mendelian Randomization Study,” published in the December 2023 issue of Endocrinology by Pleić, et al.

The relationship between thyroid function and metabolic syndrome (MetS) has been observed in observational studies, but the direction of effects and the precise causal mechanism remain unclear. For a study, researchers sought to investigate genetically predicted effects of thyroid function on MetS risk and its components, as well as the reverse direction, using large-scale summary genetic association data.

Conducted a two-sample bidirectional Mendelian randomization (MR) study using summary statistics from comprehensive genome-wide association studies (GWAS) of thyroid-stimulating hormone (TSH, n = 119,715), free thyroxine (fT4, n = 49,269), MetS (n = 291,107), and MetS components: waist circumference (n = 462,166), fasting blood glucose (n = 281,416), hypertension (n = 463,010), triglycerides (TG, n = 441,016), and high-density lipoprotein cholesterol (HDL-C, n = 403,943). The main analysis was the multiplicative random effects inverse variance weighted (IVW) method, with sensitivity analyses including weighted median and mode analysis, MR-Egger, and Causal Analysis Using Summary Effect estimates (CAUSE).

Genetically predicted higher fT4 levels were associated with a lower risk of developing MetS (OR = 0.96, P = .037). Genetically predicted fT4 was also positively associated with HDL-C (β = 0.02, P = .008), while genetically predicted TSH was positively associated with TG (β = 0.01, P = .044). These effects were consistent across different MR analyses and confirmed with the CAUSE analysis. In the reverse direction MR analysis, genetically predicted HDL-C was negatively associated with TSH (β = −0.03, P = .046) in the main IVW analysis.

The study suggested that variations in normal-range thyroid function are causally associated with MetS and lipid profile. In the reverse direction, HDL-C has a plausible causal effect on reference-range TSH levels.

Source: academic.oup.com/jcem/article-abstract/108/12/3190/7204093?redirectedFrom=fulltext