J Clin Endocrinol Metab. 2023 Jun 20:dgad371. doi: 10.1210/clinem/dgad371. Online ahead of print.
ABSTRACT
BACKGROUND: Thyroid function has been associated with metabolic syndrome (MetS) in a number of observational studies. In spite of that, the direction of effects and the exact causal mechanism of this relationship is still unknown.
METHODS: We performed a two-sample bidirectional Mendelian randomization (MR) study using summary statistics from the most comprehensive genome-wide association studies (GWAS) of thyroid-stimulating hormone (TSH, n = 119,715), free thyroxine (fT4, n = 49,269), MetS (n = 291,107), as well as components of MetS: 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). We chose the multiplicative random-effects inverse variance weighted (IVW) method as the main analysis. Sensitivity analysis included weighted median and mode analysis, as well as MR-Egger and Causal Analysis Using Summary Effect estimates (CAUSE).
RESULTS: Our results suggest that higher fT4 levels lower the risk of developing MetS (OR = 0.96, P = 0.037). Genetically predicted fT4 was also positively associated with HDL-C (β=0.02, P = 0.008), while genetically predicted TSH was positively associated with TG (β=0.01, P = 0.044). 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 = 0.046) in the main IVW analysis.
CONCLUSIONS: Our study suggests that variations in normal-range thyroid function are causally associated with the diagnosis of MetS and with lipid profile, while in the reverse direction, HDL-C has a plausible causal effect on reference-range TSH levels.
PMID:37339283 | DOI:10.1210/clinem/dgad371
