Chinese Journal of Tissue Engineering Research ›› 2026, Vol. 30 ›› Issue (3): 785-794.doi: 10.12307/2026.007
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Liu Chu1, 2, Qiu Boyuan1, Tong Siwen1, He Linyuwei1, Chen Haobo1, Ou Zhixue2
Received:
2024-11-20
Accepted:
2025-01-06
Online:
2026-01-28
Published:
2025-07-10
Contact:
Ou Zhixue, Chief physician, MD, Professor, Department of Joint and Sports Medicine, Guilin Traditional Chinese Medicine Hospital, Guilin 541000, Guangxi Zhuang Autonomous Region, China
About author:
Liu Chu, Master candidate, Graduate School of Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China; Department of Joint and Sports Medicine, Guilin Traditional Chinese Medicine Hospital, Guilin 541000, Guangxi Zhuang Autonomous Region, China
Supported by:
CLC Number:
Liu Chu, Qiu Boyuan, Tong Siwen, He Linyuwei, Chen Haobo, Ou Zhixue. A genetic perspective reveals the relationship between blood metabolites and osteonecrosis: an analysis of information from the FinnGen database in Finland[J]. Chinese Journal of Tissue Engineering Research, 2026, 30(3): 785-794.
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2.1 工具变量的选取结果 根据所设置的工具变量选择标准(P < 1×10-5,r2 < 0.001,kb=10 000,F > 10),对486种血液代谢物进行了筛选。最终获得的工具变量中,SNPs数量为3-156个,每个SNP的F值均超过10,排除了弱工具变量的影响。未发现工具变量与混杂因素相关的情况,所有工具变量均符合孟德尔随机化分析的三大核心假设,从而支持后续分析。 2.2 血液代谢物与骨坏死之间的因果效应 最初通过IVW筛选出20种血液代谢物与骨坏死之间存在潜在因果关系(PIVW < 0.05)。486种血液代谢物与骨坏死的孟德尔随机化分析结果详见图2。为进一步减少假阳性,使用错误发现率校正后,发现2种代谢物(苏氨酸酯、X-13549)的PFDR > 0.05;此外,MR-Egger法和加权中位数法分析显示,2种代谢物[5-十二碳烯酸 (12:1n7)、X-14977]的OR值方向不一致。上述4种血液代谢物均未达到筛选标准,最终确定了16种血液代谢物(包括10种已知代谢物和6种未知代谢物)与骨坏死之间存在显著的因果关系(PIVW < PFDR < 0.05),其中有8种血液代谢物有增加患骨坏死的风险(4种已知代谢物和4种未知代谢物),包括泛酸(pantothenate,OR=2.357,95%CI:1.003-5.540,PIVW=0.049,PFDR=0.049)、β-羟基异戊酸(beta-hydroxyisovalerate,OR=3.603,95%CI:1.388-9.355,PIVW=0.008,PFDR=0.042)、马尿酸盐(hippurate,OR=2.407,95%CI:1.367-4.240,PIVW=0.002,PFDR=0.024)、水杨酸葡糖苷酸(salicyluric glucuronide,OR=1.228,95%CI:1.034-1.459,PIVW=0.019,PFDR=0.043)、X-08766(OR=3.113,95%CI:1.063-9.119,PIVW=0.038,PFDR=0.048)、X-11452(OR=3.054,95%CI:1.255-7.429,PIVW=0.014,PFDR=0.04)、X-12776(OR=657.962,95%CI:5.214-83 032.178,PIVW=0.009,PFDR=0.034)、X-14662(OR=1.560,95%CI:1.108-2.195,PIVW=0.011,PFDR=0.036);另外有8种血液代谢物降低骨坏死的风险(6种已知代谢物和2种未知代谢物),包括皮质醇(cortisol,OR=0.270,95%CI:0.089-0.815,PIVW=0.02,PFDR=0.037)、1-棕榈酰甘油[1-palmitoylglycerol (1-monopalmitin),OR=0.11,95%CI:0.029-0.418,PIVW=0.001,PFDR=0.024]、焦谷氨酰甘氨酸(pyroglutamylglycine,OR=0.462,95%CI:0.222-0.964,PIVW=0.04,PFDR=0.044)、二棕榈酰甘油磷胆碱(2-stearoylglycerophosphocholine,OR=0.349,95%CI:0.138-0.881,PIVW=0.026,PFDR=0.04)、对甲酚硫酸盐(p-cresol sulfate,OR=0.580,95%CI:0.366-0.918,PIVW=0.02,PFDR=0.04)、乙硫氨酸(ergothioneine,OR=0.416,95%CI:0.181-0.956,PIVW=0.039,PFDR=0.046)、X-06307(OR=0.268,95%CI:0.091-0.719,PIVW=0.017,PFDR=0.043)、X-12092(OR=0.75,95%CI:0.575-0.978,PIVW=0.034,PFDR=0.048),见表1及图3。"
2.3.2 基因水平多效性检验 在使用MR-PRESSO方法进行分析的过程中,除代谢物X-12776由于其SNPs数目有限而无法评估外,其他所有代谢物均未显示出显著的基因水平多效性(P > 0.05),同时也没有观察到离群值的存在。为了确保结论的稳健性,还进行了MR-Egger回归截距分析,结果提示截距均接近于零,进一步确认了16种血液代谢物不存在基因水平多效性(P > 0.05)。这些结果共同证明了选定SNPs符合孟德尔随机化分析中所需的独立性和排他性假设。详细的分析结果见表2。 2.3.3 留一法分析 在进行留一法检验时,逐一排除了每个SNPs后,使用剩余的SNPs重新计算了代谢物与骨坏死之间的关联效应,并未观察到明显的离群值或整体效应估计的重大改变。这一结果表明,没有单一的SNPs对总体分析结果造成显著影响,从而进一步证实了此次研究结论的可靠性和稳健性。详细结果请参见图4。 2.4 Steiger方向性测试 通过前期的分析,确认了16种血液代谢物与骨坏死之间存在正向因果关系。进一步的Steiger方向性测试结果显示,未发现骨坏死对这16种血液代谢物有反向因果影响,每个SNP的Steiger_dir结果均为TURE,这进一步验证了正向因果关系的可靠性。"
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