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. 2023 Mar 29:14:1166740.
doi: 10.3389/fendo.2023.1166740. eCollection 2023.

The causal effects of thyroid function and lipids on cholelithiasis: A Mendelian randomization analysis

Junhong Chen  1 , Hao Zhou  1 , Hengwei Jin  1 , Kai Liu  1
Affiliations

The causal effects of thyroid function and lipids on cholelithiasis: A Mendelian randomization analysis

Junhong Chen et al. Front Endocrinol (Lausanne). .

Abstract

Objective: To investigate the relationship between function of thyroid, lipids, and cholelithiasis and to identify whether lipids mediate the causal relationship between function of thyroid and cholelithiasis.

Methods: A Mendelian randomization (MR) study of two samples was performed to determine the association of thyroid function with cholelithiasis. A two-step MR was also performed to identify whether lipid metabolism traits mediate the effects of thyroid function on cholelithiasis. A method of inverse variance weighted (IVW), weighted median method, maximum likelihood, MR-Egger, MR-robust adjusted profile score (MR-RAPS) method, and MR pleiotropy residual sum and outlier test (MR-PRESSO) methods were utilized to obtain MR estimates.

Results: The IVW method revealed that FT4 levels were correlated with an elevated risk of cholelithiasis (OR: 1.149, 95% CI: 1.082-1.283, P = 0.014). Apolipoprotein B (OR: 1.255, 95% CI: 1.027-1.535, P = 0.027) and low-density lipoprotein cholesterol (LDL-C) (OR: 1.354, 95% CI: 1.060-1.731, P = 0.016) were also correlated with an elevated risk of cholelithiasis. The IVW method demonstrated that FT4 levels were correlated with the elevated risk of apolipoprotein B (OR: 1.087, 95% CI: 1.019-1.159, P = 0.015) and LDL-C (OR: 1.084, 95% CI: 1.018-1.153, P = 0.012). Thyroid function and the risk of cholelithiasis are mediated by LDL-C and apolipoprotein B. LDL-C and apolipoprotein B had 17.4% and 13.5% of the mediatory effects, respectively.

Conclusions: We demonstrated that FT4, LDL-C, and apolipoprotein B had significant causal effects on cholelithiasis, with evidence that LDL-C and apolipoprotein B mediated the effects of FT4 on cholelithiasis risk. Patients with high FT4 levels should be given special attention because they may delay or limit the long-term impact on cholelithiasis risk.

Keywords: Mendelian randomization; cholelithiasis; lipid metabolism traits; mediation effects; thyroid function.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Effects of thyroid function on cholelithiasis. FT4 levels were correlated with an elevated risk of cholelithiasis, while TSH, hyperthyroidism, and hypothyroidism were not related to the risk of cholelithiasis.
Figure 2
Figure 2
Effects of lipids on cholelithiasis. LDL-C and apolipoprotein B levels were correlated with an elevated risk of cholelithiasis, while triglyceride was not related to the risk of cholelithiasis.
Figure 3
Figure 3
Effects of FT4 on LDL-C. FT4 levels were correlated with an elevated risk of LDL-C.
Figure 4
Figure 4
Effects of FT4 on apolipoprotein B. FT4 levels were correlated with an elevated risk of apolipoprotein B.
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