摘要
目的采用孟德尔随机化(MR)分析及现有的全基因组关联研究(GWAS)数据,探讨血尿酸水平与子痫前期之间的因果关系。方法本研究从公开的GWAS数据中获得了欧洲人群的血尿酸和子痫前期的汇总数据,应用逆方差加权法、MR-Egger法、加权中位数法、加权模式和简单模式法五种MR分析方法,评估血尿酸水平和子痫前期之间的因果关联。此外,通过初步分析和复制分析验证了结果的可靠性,并采用MR-Egger回归和Cochran’s Q检验进行敏感性分析。最后,应用GWAS-Meta分析以确定因果估计的稳健性。结果逆方差加权法的初步MR分析显示,血尿酸水平和子痫前期之间存在显著的正向因果关联(OR=1.325,95%CI:1.097~1.599,P=0.003)。其他方法的分析结果分别为:MR-Egger法(OR=1.432,95%CI:0.974~2.106,P=0.071)、加权中位数法(OR=1.301,95%CI:0.974~1.737,P=0.074)、加权模式(OR=1.236,95%CI:0.861~1.775,P=0.254)和简单模式(OR=1.896,95%CI:1.043~3.447,P=0.039)。敏感性分析中,Cochran’s Q检验提示存在异质性(P=0.042),而MR-Egger回归的截距结果显示不存在显著的水平多效性(P=0.652)。GWAS-Meta合并分析的结果同样支持血尿酸水平对子痫前期具有正向因果效应(OR=1.139,95%CI:1.049~1.236,P=0.002)。结论MR分析结果表明,血尿酸水平与子痫前期之间存在显著的正向因果关系,为血尿酸在子痫前期发生中的潜在作用提供了新的研究方向。
Objective This study aims to explore the causal relationship between serum uric acid levels and preeclampsia using Mendelian randomization(MR)analysis,and existing Genome-Wide Association Study(GWAS)data.Methods Summary data for serum uric acid levels and preeclampsia in European populations were obtained from publicly available GWAS datasets.Five MR analysis methods were employed,including inverse variance weighting(IVW),MR-Egger,weighted median,weighted mode,and simple mode,to assess the causal relationship between serum uric acid levels and preeclampsia.Preliminary analyses and replication analyses were conducted to ensure the reliabilityof the results,and sensitivity analyses were performed using MR-Egger regression and Cochran’s Q test.Finally,a GWAS Meta-analysis was applied to confirm the robustness of the causal estimates.Results The preliminary MR analysis showed a significant positive causal relationship between serum uric acid levels and preeclampsia(OR=1.325,95%CI:1.097-1.599,P=0.003)by the IVW method.Results from other methods were as follows:MR-Egger(OR=1.432,95%CI:0.974-2.106,P=0.071),weighted median(OR=1.301,95%CI:0.974-1.737,P=0.074),weighted mode(OR=1.236,95%CI:0.861-1.775,P=0.254),and simple mode(OR=1.896,95%CI:1.043-3.447,P=0.039).In the sensitivity analyses,Cochran’s Q test showed heterogeneity(P=0.042),while MR-Egger intercept results suggested no significant horizontal pleiotropy(P=0.652).The combined results of the GWAS Meta-analysis also supported a positive causal effect of serum uric acid levels on preeclampsia(OR=1.139,95%CI:1.049-1.236,P=0.002).Conclusion The MR analysis results suggest a significant positive causal relationship between uric acid levels and preeclampsia,which provides new insights into the potential role of serum uric acid in the development of preeclampsia.
作者
黄素兰
葛良清
欧阳文
HUANG Sulan;GE Liangqing;OUYANG Wen(Department of Cardiovascular Medicine,Changde Hospital,Xiangya School of Medicine,Central South University/The First People’s Hospital of Changde City,Changde,Hunan 415000,China;Department of Medical Administration,Changde Hospital,Xiangya School of Medicine,Central South University/The First People’s Hospital of Changde City,Changde,Hunan 415000,China)
出处
《中国优生与遗传杂志》
2025年第3期506-512,共7页
Chinese Journal of Birth Health & Heredity
基金
湖南省自然科学基金项目(2024JJ7007)
常德市科技创新指导性项目(2024ZD129、2024ZD272)。
关键词
血尿酸水平
子痫前期
孟德尔随机化
因果关系
全基因组关联研究
serum uric acid level
preeclampsia
Mendelian randomization
causal relationship
genome-wide association study
