基于孟德尔随机化及生物信息学分析女童初潮年龄与成人体重指数的关系及关键基因、通路  

Relationship,key genes,and pathways between age of menarche in girls and adult body mass index based on two-sample Mendelian randomization and bioinformatics analysis

作　　者：董涵宇 丛明 董丹[3] 王雪峰[3] DONG Hanyu;CONG Ming;DONG Dan;WANG Xuefeng(The First Clinical College,Liaoning University of Traditional Chinese Medicine,Liaoning Province,Shenyang110847,China;Graduate School,Liaoning University of Traditional Chinese Medicine,Liaoning Province,Shenyang110847,China;Department of Pediatric,Affiliated Hospital of Liaoning Univesrity of Traditional Chinese Medicine,Liaoning Province,Shenyang110000,China)

机构地区：[1]辽宁中医药大学第一临床学院,辽宁沈阳110847 [2]辽宁中医药大学研究生学院,辽宁沈阳110847 [3]辽宁中医药大学附属医院儿科,辽宁沈阳110000

出　　处：《中国医药导报》2024年第28期130-137,共8页China Medical Herald

摘　　要：目的探讨女童初潮年龄与成人体重指数(BMI)的关系及关键基因、通路。方法从IEU Open GWAS数据库中得到初潮年龄和成人BMI的汇总统计数据集,将初潮年龄作为暴露因素,成人BMI为结局变量。采用孟德尔随机化方法分析初潮年龄与成人BMI的因果关系。使用Gene Cards、Pharm GKB数据库分析初潮年龄和成人BMI的交集靶点,Cytoscape软件构建核心网络,Metascape在线数据库进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)通路分析。结果随机效应逆方差加权(IVW)法结果显示,初潮年龄与成人BMI呈负相关(OR=0.812,P<0.001);加权中位数法、加权模式法支持此结果。敏感性分析结果显示,结果存在一定的异质性,但本研究使用随机效应IVW法,对结果无影响;结果不存在多效性;不存在某个单核苷酸多态性单独对因果关系产生显著影响。初潮年龄与成人BMI交集靶点共765个,核心靶点为MAPK1、MAPK3、AKT1等。GO富集分析发现,生物学过程包含对激素的反应、激素水平调节等,细胞组成包含受体复合物、神经元胞体等,分子功能包含信号受体调节剂活性、受体配体活性等。KEGG通路分析发现,通路涉及神经活性配体-受体相互作用、TGF-β信号通路、卵巢类固醇生成等。结论遗传预测女童初潮年龄和成人BMI存在负向因果关联,可能通过MAPK1等关键基因,神经活性相关信号通路等关键通路发挥作用。Objective To explore the relationship,key genes,and pathways between age of menarche in girls and adult body mass index(BMI).Methods A summary statistical set of age of menarche and adult BMI was obtained from the IEU Open-GWAS database.Age of menarche was used as exposure factor and adult BMI as outcome variable.The causal relationship between age of menarche and adult BMI was analyzed by Mendelian randomization method.The intersection targets of age at menarche and adult BMI were analyzed using GeneCards and PharmGKB databases,the core network was constructed by Cytoscape software,and the Metascape online database was used for gene ontology(GO)enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Results Random effect inverse variance weighted(IVW)method showed that age of menarche was negatively correlated with adult BMI(OR=0.812,P<0.001),weighted median method and weighted model method supported this result.Sensitivity analysis showed that there was some heterogeneity in the results,but the random effect IVW method was used in this study,which had no effect on the results;there was no pleiotropy in the results;and no single nucleotide polymorphism had a significant effect on causation.There were 765 intersection targets of age at menarche and adult BMI,and the core targets were MAPK1,MAPK3,AKT1,etc..GO enrichment analysis found that biological processes include hormone response and hormone level regulation,etc.,cell composition includes receptor complex and neuron cell body,etc.,and molecular functions include signal receptor modulator activity and receptor ligand activity etc..KEGG pathway analysis revealed that the pathway involved neuroactive ligand-receptor interaction,TGF-βsignaling pathway,and ovarian steroid production,etc..Conclusion Genetic prediction of age of menarche and adult BMI in girls has a negative causal association,which may play a role through key pathways such as MAPK1 and neural activity related signaling pathways.

关 键 词：初潮年龄 体重指数 孟德尔随机化 因果关系 生物信息学 

分 类 号：R725.8[医药卫生—儿科]