Xie Fang, Zheng Wenkai, Chen Jing, Yao Chuanxia, Li Cong, Tang Li, Li Ping, Tan Shanzhong
Department of Integrated TCM and Western Medicine, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.
Department of Liver Disease, Jinling Hospital Affiliated to Medical College of Nanjing University, Nanjing, Jiangsu Province, China.
J Diabetes Investig. 2025 May;16(5):917-928. doi: 10.1111/jdi.14413. Epub 2025 Mar 7.
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.
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.
Elevated levels of genetically predicted phosphatidylcholine (16:0_16:1) [OR = 2.638, 95% CI 1.557-4.469, P = 3.11 × 10], phosphatidylcholine (16:1_18:0) (OR = 2.644, 95% CI 1.559-4.486, P = 3.11 × 10), triacylglycerol (46:2) (OR = 2.515, 95% CI 1.524-4.153, P = 3.11 × 10), and triacylglycerol (48:2) (OR = 1.863, 95% CI 1.300-2.669, P = 6.95 × 10) 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.
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.
血浆脂质组全基因组关联研究数据的最新进展加深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性肝病（MAFLD）的风险评估，超越了传统脂质生物标志物。
本研究利用孟德尔随机化（MR）评估13个子类中的179种脂质与MAFLD之间的因果关系，主要采用Wald比率和IVW方法。使用错误发现率（FDR）进行校正，并辅以贝叶斯共定位分析。
遗传预测的磷脂酰胆碱（16:0_16:1）[优势比（OR）=2.638，95%置信区间（CI）1.557 - 4.469，P = 3.11×10]、磷脂酰胆碱（16:1_18:0）（OR = 2.644，95% CI 1.559 - 4.486，P = 3.11×10）、三酰甘油（46:2）（OR = 2.515，95% CI 1.524 - 4.153，P = 3.11×10）和三酰甘油（48:2）（OR = 1.863，95% CI 1.300 - 2.669，P = 6.95×10）水平升高与MAFLD风险增加显著相关，GCKR基因内的rs1260326起关键作用。共定位分析表明，在显著证据中，假设4的后验概率超过80%，确定rs780093为共享因果变异。此外，还确定了16个提示性证据。
该研究证实了特定脂质分子在影响MAFLD风险中的重要作用，为未来治疗策略提供了新的科学依据和潜在治疗靶点。
