The Causal Relationship between Lipid Metabolites and Multiple Myeloma Risk: A Mendelian Randomization Study.

IF 1.1 4区医学 Q3 HEMATOLOGY

Acta Haematologica Pub Date : 2025-10-16 DOI:10.1159/000548566

Jian Tao, Ling Wang, Zheyun Gu

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引用次数: 0

Abstract

Introduction: Research has demonstrated a potential link between lipid metabolites and multiple myeloma (MM); however, the causal relationship remains uncertain. This Mendelian randomization (MR) study aimed to explore the potential causal relationship between lipid metabolites and MM.

Methods: In this study, data on lipid metabolites were obtained from a genome-wide association study of metabolites in blood samples from 7,824 Europeans. Genetic information related to MM came from the UK Biobank database, encompassing 601 patients with MM and 372,016 control samples. In this MR analysis, inverse-variance weighted method was used as the primary analysis method; MR Egger and weighted median were employed as complementary approaches. Sensitivity analyses were conducted using the Cochran Q test, MR-Egger intercept, MR-PRESSO, and leave-one-out analysis.

Results: A total of 121 human lipid metabolites were analyzed in this MR study. The analysis result revealed that 1-docosahexaenoyl-glycerophosphocholine [odds ratio (OR) = 1.0059, 95% confidence interval (CI) 1.0043-1.0076, P < 0.01 , FDR = 0.12], tetradecanedioate (OR = 1.0007, 95% CI 1-1.0013, P = 0.0498 , FDR = 0.23), and X-12990-docosapentaenoic acid (OR = 1.0029, 95% CI 1.0015-1.0044, P < 0.01 , FDR = 0.15) were linked to an increased risk of MM. As for palmitoleate (OR = 0.9972, 95% CI 0.9947-0.9997, P = 0.0299 , FDR = 0.19) , a nominal inverse association was observed. None of these associations reached statistical significance after FDR correction (all FDR > 0.05). Sensitivity analyses verified the robustness of these nominally significant results.

Conclusion: Genetic evidence demonstrated nominal associations of 1-docosahexaenoyl-sn-glycero-3-phosphocholine, tetradecanedioate, X-12990-eicosapentaenoic acid, and palmitoleate with MM risk, though these did not survive FDR correction. While these findings suggest potential metabolic pathways in MM pathogenesis, further validation is required before considering these compounds as biomarkers for clinical screening or drug target selection.

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脂质代谢物与多发性骨髓瘤风险的因果关系：一项孟德尔随机研究。

研究表明脂质代谢物与多发性骨髓瘤（MM）之间存在潜在联系；然而，因果关系仍然不确定。这项孟德尔随机化（MR）研究旨在探讨脂质代谢物与mm之间的潜在因果关系。方法：在这项研究中，脂质代谢物的数据来自7824名欧洲人血液样本的全基因组关联研究。与MM相关的遗传信息来自UK Biobank数据库，包括601例MM患者和372016例对照样本。在MR分析中，采用反方差加权法作为主要分析方法；采用MR Egger和加权中位数作为补充方法。采用Cochran Q检验、MR-Egger截距、MR-PRESSO和留一分析进行敏感性分析。结果：本MR研究共分析了121种人脂质代谢物。分析结果显示,1-docosahexaenoyl-glycerophosphocholine(比值比(或)= 1.0059,95%可信区间(CI) 1.0043 - -1.0076, P < 0.01,罗斯福= 0.12),tetradecanedioate (OR = 1.0007, 95% CI 1 - 1.0013, P = 0.0498,罗斯福= 0.23),和x - 12990 docosapentaenoic酸(OR = 1.0029, 95% CI 1.0015 - -1.0044, P < 0.01,罗斯福= 0.15)的风险增加有关毫米。至于palmitoleate (OR = 0.9972, 95% CI 0.9947 - -0.9997, P = 0.0299,罗斯福= 0.19),观察到名义上的负相关。经FDR校正后，这些相关性均无统计学意义（均为FDR 0.05）。敏感性分析验证了这些名义上显著的结果的稳健性。结论：遗传证据表明，1-二十二碳六烯醇-sn-甘油-3-磷酸胆碱、十四烯二酸、x -12990-二十碳五烯酸和棕榈油酸与MM风险有一定的关联，尽管这些都没有在罗斯福总统的纠正中幸存下来。虽然这些发现提示了MM发病机制中潜在的代谢途径，但在考虑将这些化合物作为临床筛选或药物靶点选择的生物标志物之前，还需要进一步验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Haematologica 医学-血液学

CiteScore

4.90

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Acta Haematologica'' is a well-established and internationally recognized clinically-oriented journal featuring balanced, wide-ranging coverage of current hematology research. A wealth of information on such problems as anemia, leukemia, lymphoma, multiple myeloma, hereditary disorders, blood coagulation, growth factors, hematopoiesis and differentiation is contained in first-rate basic and clinical papers some of which are accompanied by editorial comments by eminent experts. These are supplemented by short state-of-the-art communications, reviews and correspondence as well as occasional special issues devoted to ‘hot topics’ in hematology. These will keep the practicing hematologist well informed of the new developments in the field.