Study of the causal relationship between thyroid dysfunction and urolithiasis through two-sample Mendelian randomization

ZHAO Benlong; ZHAO Lunjie; WEI Yangyang; PAN Jinsheng; SHI Xiuquan; YANG Liusheng; XIONG Zhaohui

doi:10.3969/j.issn.1004-3594.2026.05.006

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Medical Journal of the Chinese People Armed Police Forces ›› 2026, Vol. 37 ›› Issue (5) : 398-405. DOI: 10.3969/j.issn.1004-3594.2026.05.006

ORIGINAL ARTICLES

Study of the causal relationship between thyroid dysfunction and urolithiasis through two-sample Mendelian randomization

ZHAO Benlong¹, ZHAO Lunjie¹, WEI Yangyang¹, PAN Jinsheng¹, SHI Xiuquan¹, YANG Liusheng², XIONG Zhaohui¹

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Abstract

Objective To explore the causal relationship between thyroid disorders and urolithiasis through Mendelian randomization (MR). Methods Data on hyperthyroidism, hypothyroidism, thyroid cancer, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine/free thyroxine (FT₃/FT₄), and urolithiasis were collected from large-scale genome-wide association studies (GWAS). A two-sample MR analysis was conducted. The study included data from individuals of European ancestry. Causal associations between thyroid disorders and urolithiasis were assessed using inverse variance weighting (IVW), MR-Egger regression, weighted median, and weighted mode methods. Cochran’s test was used to evaluate heterogeneity, and the MR-Egger intercept test was applied to assess horizontal pleiotropy. The MR-PRESSO method was employed to detect and correct potential outlier instrumental variables. Results The IVW method showed a negative causal relationship between hypothyroidism and urolithiasis, indicating that hypothyroidism could reduce the risk of urolithiasis (OR=0.939, 95% CI=0.8823-0.9993, P=0.047). No causal associations were observed between hyperthyroidism, thyroid cancer, serum TSH, FT₄, FT₃/FT₄ and the risk of urolithiasis. No significant heterogeneity or horizontal pleiotropy was detected. Conclusions There is a potential causal relationship between hypothyroidism and urolithiasis.

Key words

urolithiasis / hypothyroidism / hyperthyroidism / Mendelian randomization / causal relationship

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ZHAO Benlong, ZHAO Lunjie, WEI Yangyang, PAN Jinsheng, SHI Xiuquan, YANG Liusheng, XIONG Zhaohui. Study of the causal relationship between thyroid dysfunction and urolithiasis through two-sample Mendelian randomization[J]. Medical Journal of the Chinese People Armed Police Forces. 2026, 37(5): 398-405 https://doi.org/10.3969/j.issn.1004-3594.2026.05.006

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