Fang Xie, Wenkai Zheng, Jing Chen, Chuanxia Yao, Cong Li, Li Tang, Ping Li, Shanzhong Tan
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Corrections were made using false discovery rate (FDR), supplemented by Bayesian colocalization analysis.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Elevated levels of genetically predicted phosphatidylcholine (16:0_16:1) [OR<sub>Wald ratio</sub> = 2.638, 95% CI 1.557–4.469, <i>P</i> = 3.11 × 10<sup>−4</sup>], phosphatidylcholine (16:1_18:0) (OR<sub>Wald ratio</sub> = 2.644, 95% CI 1.559–4.486, <i>P</i> = 3.11 × 10<sup>−4</sup>), triacylglycerol (46:2) (OR<sub>Wald ratio</sub> = 2.515, 95% CI 1.524–4.153, <i>P</i> = 3.11 × 10<sup>−4</sup>), and triacylglycerol (48:2) (OR<sub>IVW</sub> = 1.863, 95% CI 1.300–2.669, <i>P</i> = 6.95 × 10<sup>−4</sup>) were significantly associated with increased MAFLD risk, with rs1260326 within the GCKR gene playing a crucial role. Colocalization analysis indicated that in significant evidences, the posterior probability for hypothesis 4 was over 80%, identifying rs780093 as a shared causal variant. Additionally, 16 suggestive evidences were identified.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>The study confirmed the significant role of specific lipid molecules in influencing MAFLD risk, providing new scientific bases and potential therapeutic targets for future treatment strategies.</p>\n </section>\n </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 5","pages":"917-928"},"PeriodicalIF":3.1000,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14413","citationCount":"0","resultStr":"{\"title\":\"Revisiting the causal impact of lipid traits on metabolic dysfunction-associated fatty liver disease: Insights from a multidimensional plasma lipid profile\",\"authors\":\"Fang Xie, Wenkai Zheng, Jing Chen, Chuanxia Yao, Cong Li, Li Tang, Ping Li, Shanzhong Tan\",\"doi\":\"10.1111/jdi.14413\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aims</h3>\\n \\n <p>Recent advancements in plasma lipidomes genome-wide association studies data have enhanced our understanding of lipid categories, significantly improving risk assessments for metabolic dysfunction-associated fatty liver disease (MAFLD) beyond traditional lipid biomarkers.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Materials and Methods</h3>\\n \\n <p>This study utilized Mendelian randomization (MR) to assess the causal relationships between 179 lipid species across 13 subclasses and MAFLD, primarily using the Wald ratio and IVW methods. 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引用次数: 0
摘要
目的：血浆脂质组全基因组关联研究数据的最新进展增强了我们对脂质类别的理解，显著改善了代谢功能障碍相关脂肪肝（MAFLD）的风险评估，超越了传统的脂质生物标志物。材料和方法：本研究利用孟德尔随机化（MR）来评估13个亚类179种脂质与MAFLD之间的因果关系，主要使用Wald比和IVW方法。使用错误发现率（FDR）进行修正，并辅以贝叶斯共定位分析。结果:遗传预测的磷脂酰胆碱（16:0 ~ 16:1）[ORWald比值= 2.638,95% CI 1.557 ~ 4.469, P = 3.11 × 10-4]、磷脂酰胆碱（16:1_18:0）（ORWald比值= 2.644,95% CI 1.559 ~ 4.486, P = 3.11 × 10-4）、三酰基甘油（46:2）（ORWald比值= 2.515,95% CI 1.524 ~ 4.153, P = 3.11 × 10-4）和三酰基甘油（48:2）（ORIVW = 1.863, 95% CI 1.300 ~ 2.669, P = 6.95 × 10-4）水平升高与MAFLD风险增加显著相关。其中GCKR基因中的rs1260326起着至关重要的作用。共定位分析表明，在显著性证据中，假设4的后验概率大于80%，表明rs780093是一个共有的因果变异。此外，还发现了16个暗示性证据。结论：本研究证实了特异性脂质分子在影响MAFLD风险中的重要作用，为今后的治疗策略提供了新的科学依据和潜在的治疗靶点。
Revisiting the causal impact of lipid traits on metabolic dysfunction-associated fatty liver disease: Insights from a multidimensional plasma lipid profile
Aims
Recent advancements in plasma lipidomes genome-wide association studies data have enhanced our understanding of lipid categories, significantly improving risk assessments for metabolic dysfunction-associated fatty liver disease (MAFLD) beyond traditional lipid biomarkers.
Materials and Methods
This study utilized Mendelian randomization (MR) to assess the causal relationships between 179 lipid species across 13 subclasses and MAFLD, primarily using the Wald ratio and IVW methods. Corrections were made using false discovery rate (FDR), supplemented by Bayesian colocalization analysis.
Results
Elevated levels of genetically predicted phosphatidylcholine (16:0_16:1) [ORWald ratio = 2.638, 95% CI 1.557–4.469, P = 3.11 × 10−4], phosphatidylcholine (16:1_18:0) (ORWald ratio = 2.644, 95% CI 1.559–4.486, P = 3.11 × 10−4), triacylglycerol (46:2) (ORWald ratio = 2.515, 95% CI 1.524–4.153, P = 3.11 × 10−4), and triacylglycerol (48:2) (ORIVW = 1.863, 95% CI 1.300–2.669, P = 6.95 × 10−4) were significantly associated with increased MAFLD risk, with rs1260326 within the GCKR gene playing a crucial role. Colocalization analysis indicated that in significant evidences, the posterior probability for hypothesis 4 was over 80%, identifying rs780093 as a shared causal variant. Additionally, 16 suggestive evidences were identified.
Conclusion
The study confirmed the significant role of specific lipid molecules in influencing MAFLD risk, providing new scientific bases and potential therapeutic targets for future treatment strategies.
期刊介绍：
Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).
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