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血清代谢物对虹膜睫状体炎风险的影响:一项双向孟德尔随机化研究。

Effect of serum metabolites on the risk of iridocyclitis: a bidirectional Mendelian randomization study.

机构信息

Changsha Aier Eye Hospital, Changsha, Hunan Provine, 410015, China.

Shenzhen Aier Eye Hospital, Aier Eye Hospital, Jinan University, Shenzhen, Guangdong Provine, 518000, China.

出版信息

Sci Rep. 2024 May 8;14(1):10535. doi: 10.1038/s41598-024-61441-4.

Abstract

Previous research has linked serum metabolite levels to iridocyclitis, yet their causal relationship remains unexplored. This study investigated this potential causality by analyzing pooled data from 7824 iridocyclitis patients in a Genome-Wide Association Study (GWAS) using Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC). Employing rigorous quality control and comprehensive statistical methods, including sensitivity analyses, we examined the influence of 486 serum metabolites on iridocyclitis. Our MR analysis identified 23 metabolites with significant causal effects on iridocyclitis, comprising 17 known and 6 unidentified metabolites. Further refinement using Cochran's Q test and MR-PRESSO indicated 16 metabolites significantly associated with iridocyclitis risk. LDSC highlighted the heritability of certain metabolites, underscoring genetic influences on their levels. Notably, tryptophan, proline, theobromine, and 7-methylxanthine emerged as risk factors, while 3,4-dihydroxybutyrate appeared protective. These findings enhance our understanding of the metabolic interactions in iridocyclitis, offering insights for diagnosis, unraveling pathophysiological mechanisms, and informing potential avenues for prevention and personalized treatment.

摘要

先前的研究已经将血清代谢物水平与虹膜炎相关联,但它们之间的因果关系仍未得到探索。本研究通过使用孟德尔随机化 (MR) 和连锁不平衡得分回归 (LDSC) 分析来自 7824 名虹膜炎患者的全基因组关联研究 (GWAS) 的汇总数据,调查了这种潜在的因果关系。我们采用了严格的质量控制和全面的统计方法,包括敏感性分析,研究了 486 种血清代谢物对虹膜炎的影响。我们的 MR 分析确定了 23 种代谢物对虹膜炎有显著的因果影响,其中包括 17 种已知和 6 种未知代谢物。进一步使用 Cochran's Q 检验和 MR-PRESSO 进行细化分析表明,有 16 种代谢物与虹膜炎风险显著相关。LDSC 强调了某些代谢物的遗传性,表明遗传因素对其水平有影响。值得注意的是,色氨酸、脯氨酸、可可碱和 7-甲基黄嘌呤是风险因素,而 3,4-二羟基丁酸则具有保护作用。这些发现提高了我们对虹膜炎中代谢物相互作用的理解,为诊断、揭示病理生理机制提供了新视角,并为预防和个性化治疗提供了潜在途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1d4/11078962/a37434f5d873/41598_2024_61441_Fig1_HTML.jpg

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