甲状腺炎和人类血液代谢产物:一项孟德尔随机研究。

IF 1.5 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Lijie Shao, Siqi Liu, Yongfu Song, Shaoyu Han, Yue Ma, Yang Kunpeng, Jingbin Zhang, Bingxue Qi, Yan Guo, Xiaodan Lu
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引用次数: 0

摘要

背景:甲状腺炎是一种病因复杂的炎症性疾病,其危险因素尚不清楚。血液代谢物在甲状腺炎发展过程中发生变化,提示血液代谢物与甲状腺炎进展密切相关。然而,缺乏因果关系的证据。我们采用孟德尔随机化(MR)方法系统地研究了血液代谢物谱与两种临床不同甲状腺炎表型(亚急性甲状腺炎和自身免疫性甲状腺炎)之间假定的因果关系,为其代谢基础提供了见解。方法:我们分析了全基因组关联研究(GWAS)中来自8800万芬兰生物银行参与者的基因组和健康数据。主要分析方法为随机效应反方差加权法(IVW),辅之以加权中位数法(WME)和Mr-Egger。我们实施了综合敏感性分析,包括科克伦Q检验、艾格先生截距、留一分析(LOO)和Mr-PRESSO,以评估异质性、多效性和异常值。扩展的遗传研究包括连锁不平衡评分回归(LDSC)方法、多变量Mr (MVMR)和代谢途径分析,以提供更深入的机制见解。结果:10种代谢物与自身免疫性甲状腺炎相关,15种与亚急性甲状腺炎相关。壬烷酸酯(19:0)和1-棕榈酰甘油磷酸肌醇*直接影响亚急性甲状腺炎。MVMR分析发现,天竺酸盐(9:0)、肉碱和ADpSGEGDFXAEGGGVR*对自身免疫性甲状腺炎具有独立和直接的作用。此外,代谢途径如新霉素、卡那霉素和庆大霉素的生物合成、组氨酸代谢、淀粉和蔗糖代谢与自身免疫性甲状腺炎有关,而苯丙氨酸、酪氨酸、色氨酸的生物合成、苯丙氨酸代谢和精氨酸的生物合成与亚急性甲状腺炎有关。结论:我们的研究结果建立了循环代谢物与甲状腺炎之间的因果关系,通过整合基因组学和代谢组学分析揭示了新的机制见解。这些结果不仅促进了我们对甲状腺炎发病机制的理解,而且为疾病筛查和干预治疗提供了潜在的生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Thyroiditis and human blood metabolites: A mendelian randomization study.

Thyroiditis and human blood metabolites: A mendelian randomization study.

Thyroiditis and human blood metabolites: A mendelian randomization study.

Thyroiditis and human blood metabolites: A mendelian randomization study.

Background: The risk factors for thyroiditis, an inflammatory disease with a complex etiology, remain poorly understood. Blood metabolites are known to change during thyroiditis development, suggesting a close relationship between blood metabolites and thyroiditis progression. However, evidence for a causal link is lacking. We employed Mendelian randomization (MR) methodology to systematically investigate the putative causal relationships between blood metabolite profiles and two clinically distinct thyroiditis phenotypes-subacute and autoimmune thyroiditis-providing insights into their metabolic underpinnings.

Methods: We analyzed genomic and health data from 88 million Finnish Biobank participants in the Genome-Wide Association Study (GWAS). The primary analytical method was random-effects inverse variance weighting (IVW), supplemented by the weighted median method (WME) and Mr-Egger. We implemented comprehensive sensitivity analyses encompassing Cochran's Q test, Mr-Egger intercept, leave-one-out analysis (LOO), and Mr-PRESSO to assess heterogeneity, pleiotropy, and outliers. Extended genetic investigations incorporated the linkage disequilibrium score regression (LDSC) method, multivariable Mr (MVMR), and metabolic pathway analyses to provide deeper mechanistic insights.

Results: Ten metabolites were significantly associated with autoimmune thyroiditis, and fifteen with subacute thyroiditis. Nonadecanoate (19:0) and 1-palmitoylglycerophosphoinositol* were found to directly affect subacute thyroiditis. MVMR analyses identified pelargonate (9:0), carnitine, and ADpSGEGDFXAEGGGVR* as having an independent and direct effect on autoimmune thyroiditis. Additionally, metabolic pathways such as neomycin, kanamycin, and gentamicin biosynthesis, histidine metabolism, and starch and sucrose metabolism were linked to autoimmune thyroiditis, while phenylalanine, tyrosine, tryptophan biosynthesis, phenylalanine metabolism, and arginine biosynthesis were associated with subacute thyroiditis.

Conclusions: Our findings establish causal relationships between circulating metabolites and thyroiditis, revealing novel mechanistic insights through integrated genomic and metabolomic analyses. These results not only advance our understanding of thyroiditis pathogenesis but also suggest potential biomarkers for disease screening and therapeutic targets for intervention.

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来源期刊
Journal of Medical Biochemistry
Journal of Medical Biochemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
3.00
自引率
12.00%
发文量
60
审稿时长
>12 weeks
期刊介绍: The JOURNAL OF MEDICAL BIOCHEMISTRY (J MED BIOCHEM) is the official journal of the Society of Medical Biochemists of Serbia with international peer-review. Papers are independently reviewed by at least two reviewers selected by the Editors as Blind Peer Reviews. The Journal of Medical Biochemistry is published quarterly. The Journal publishes original scientific and specialized articles on all aspects of clinical and medical biochemistry, molecular medicine, clinical hematology and coagulation, clinical immunology and autoimmunity, clinical microbiology, virology, clinical genomics and molecular biology, genetic epidemiology, drug measurement, evaluation of diagnostic markers, new reagents and laboratory equipment, reference materials and methods, reference values, laboratory organization, automation, quality control, clinical metrology, all related scientific disciplines where chemistry, biochemistry, molecular biology and immunochemistry deal with the study of normal and pathologic processes in human beings.
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