Exploration of the Causal Relationship between
Metabolic Syndrome and Its Components and Thyroid Diseases Based on Mendelian
Randomization

doi:10.1009-0959.2026.010005

Abstract

Abstract:

Objective： This study utilized Mendelian randomization （MR） analysis to investigate the causal relationships between （Metabolic syndrome） MetS and its individual components and common thyroid diseases.Methods： Genetic instrumental variables were selected based on single nucleotide polymorphisms （SNPs） associated with MetS， its components， and thyroid dysfunction， extracted from publicly available genome-wide association study （GWAS） summary datasets of European ancestry populations. The inverse-variance weighted （IVW） method was employed as the primary analytical approach to estimate causal effects， supplemented by MR-Egger regression， weighted median， and weighted mode methods. False discovery rate （FDR） correction was applied to account for multiple testing， followed by comprehensive sensitivity analyses to assess the validity of instrumental variables and the robustness of results. In cases where a significant forward association was observed， reverse MR analyses were conducted to evaluate bidirectional causality.Results： Following FDR correction， robust associations indicated that MetS was causally associated with an increased risk of thyroid cancer （OR=1.51， 95%CI=1.11-2.05， P_FDR=0.039）， hypothyroidism （OR=1.02， 95%CI=1.01-1.02， P_FDR=4.80×10^-9）， and Hashimoto's thyroiditis （OR=1.72， 95%CI=1.43-2.07， P_FDR=5.54×10^-8）. Additionally， elevated waist circumference was identified as a causal risk factor for hypothyroidism （OR=1.02， 95%CI=1.01-1.02， P_FDR=1.09×10^-23） and Hashimoto's thyroiditis （OR=1.55， 95%CI=1.35-1.78， P_FDR=4.80×10^-9）， while hypertension was significantly associated with an increased risk of Hashimoto's thyroiditis （OR=2.63， 95%CI=1.85-3.73， P_FDR=3.59×10^-7）. Reverse MR analyses yielded no significant associations， supporting the directionality of the observed effects. Sensitivity analyses confirmed the reliability and robustness of the findings， with no evidence of substantial pleiotropy or bias.Conclusion： This study provides evidence of positive causal associations between MetS and thyroid cancer， hypothyroidism， and Hashimoto's thyroiditis； between waist circumference and both hypothyroidism and Hashimoto's thyroiditis； and between hypertension and Hashimoto's thyroiditis. These findings suggest that monitoring MetS and its constituent components may serve as a valuable strategy for the early identification and prevention of specific thyroid disorders.

Key words: Metabolic syndrome； , Thyroid disorders； , Mendelian randomization； , Causal association

CLC Number:

R581

ZHAO Liang, LI Jiarui, ZHAO Boyan, SUN Shude, DU Likun.

Exploration of the Causal Relationship between Metabolic Syndrome and Its Components and Thyroid Diseases Based on Mendelian Randomization [J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2026, 28(4): 431-431-439.

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Exploration of the Causal Relationship between Metabolic Syndrome and Its Components and Thyroid Diseases Based on Mendelian Randomization

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