A bi-directional Mendelian randomization study on the causal association of blood metabolites with hyperthyroidism and hypothyroidism
10.3760/cma.j.cn311282-20240611-00254
- VernacularTitle:血液代谢物与甲状腺功能亢进、减退之间因果关联的双向孟德尔随机化研究
- Author:
Qingyong CHEN
1
;
Liqiang LIN
;
Zhipeng CHEN
;
Huaiqing LYU
;
Qiang SHAO
Author Information
1. 滨州医学院第二临床医学院耳鼻咽喉头颈外科，烟台 264003
- Publication Type:Journal Article
- Keywords:
Mendelian randomization;
Hyperthyroidism;
Hypothyroidism;
Blood metabolites;
Causal relationship
- From:
Chinese Journal of Endocrinology and Metabolism
2025;41(4):305-315
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the causal relationship between 1 400 blood metabolites and hyperthyroidism or hypothyroidism by using Mendelian randomization(MR) approach.Methods:This study employed a bi-directional Mendelian randomization analysis and sourced data of blood metabolites related to hyperthyroidism and hypothyroidism from the genome-wide association study(GWAS) database. R software and TwoSampleMR software package were used for analysis. The inverse variance weighting method(IVW) was used as the main method, and MR-Egger regression, weighted median method, simple mode and weighted mode were used as supplementary methods to analyze the causal relationship between blood metabolites and hyperthyroidism and hypothyroidism. The false-positive rate was corrected by false discovery rate(FDR, FDR<0.2) to control for false positives; Meta-analysis of different sample pools was performed for overall assessment. Results:The analysis found three blood metabolites significantly linked to hypothyroidism: pregnenediol disulfate(IVW: OR=1.068, 95% CI 1.032-1.106, P<0.001), 1-(1-enyl-palmitoyl)-2-linoleoyl-GPE(IVW: OR=0.891, 95% CI 0.840-0.944, P<0.001), and linoleic-arachidonic glycerin(IVW: OR =0.923, 95% CI 0.885-0.963, P<0.001). Glutamine was also noted(IVW: OR=0.998, 95% CI 0.997-0.999, P<0.001). Reverse MR showed no significant correlation between hyperthyroidism and the four metabolites(IVW: P>0.05). Validation from FinnGen Biospecimen Library and UKB Biospecimen Library confirmed these findings. Conclusions:Among 1 400 blood metabolites, pregnenediol disulfate showed a positive correlation with hypothyroidism. In contrast, 1-(1-enyl-palmitoyl)-2-linoleoyl-GPE and linoleic-arachidonic glycerin exhibited negative correlations with hypothyroidism, while glutamine showed a negative correlation with hyperthyroidism. This study offers insights into the pathogenesis, early screening, and treatment of hyperthyroidism and hypothyroidism.
