中华骨质疏松和骨矿盐疾病杂志2025，Vol.18Issue(5)：565-579,15.DOI:10.3969/j.issn.1674-2591.2025.05.007
基于孟德尔随机化探讨氨基酸代谢及代谢途径与骨质疏松症的因果关系
Causal relationship between amino acid metabolism and metabolic pathway and osteoporosis based on Mendelian randomization
摘要
Abstract
Objective To investigate the potential causal relationships between amino acid metabolism/metabolic pathways and osteoporosis(OP)using two-sample Mendelian randomization(TSMR)analysis.Methods To-tally 50 amino acid metabolism and metabolic pathway data in individuals of European ancestry from the Genome-Wide As-sociation Study Catalog(GWAS Catalog)database were used as exposure data.OP data(ukb-b-12141)from the Integra-tive Epidemiology Unit(IEU)database were used as outcome variables.Single nucleotide polymorphisms(SNPs)asso-ciated with exposure data were selected as instrumental variables.R language and Mendelian randomization(MR)pack-age were used to conduct the study.TSMR analyses were performed via inverse variance weighted(IVW),MR-Egger regression,weighted median estimator(WME),simple mode and weighted mode methods.Causal relationships were e-valuated using odds ratios(OR).Cochran's Q heterogeneity test was conducted via IVW and MR-Egger regression.Plei-otropy was assessed using the MR_pleiotropy_test function and Mendelian randomization pleiotropy residual sum and outlier test(MR_PRESSO).Sensitivity analysis was performed using the MR leaveoneout plot function.F-statistics were calculated to detect weak instrument bias.Results A total of 2 457 SNPs were identified as instrumental variables for 50 amino acid metabolism and metabolic pathway data(P＜5×10-6).TSMR analysis revealed that 6 amino acids/metabolic pathway products were significantly associated with OP.They were glutamine(Gln)(OR=0.994,95%CI:0.989-0.999,P=0.016),and methionine(Met)(OR=0.989,95%CI:0.979-0.999,P=0.039),which were negatively correlated with OP;lysine(Lys)(OR=1.022,95%CI:1.001-1.042,P=0.036),arginine(Arg)(OR=1.002,95%CI:1.000-1.004,P=0.031),alanine(Ala)(OR=1.020,95%CI:1.005-1.035,P=0.008),kynurenine(Kyn)(OR=1.011,95%CI:1.001-1.021,P=0.035),which were positively correlated with OP.Conclusion To investigate the causal relationship of amino acid metabolism and metabolic pathways with OP by TSMR analysis,it is found that Gln and Met were negatively associated with OP,while Lys,Arg,Ala and Kyn were positively associated with OP.关键词
孟德尔随机化/氨基酸/单核苷酸多态性/骨质疏松症Key words
Mendelian randomization/amino acid/single nucleotide polymorphism/osteoporosis分类
医药卫生引用本文复制引用
王晨秀,林安华,何文静,黄水金,童露露,邓颖,张娜,霍亚南..基于孟德尔随机化探讨氨基酸代谢及代谢途径与骨质疏松症的因果关系[J].中华骨质疏松和骨矿盐疾病杂志,2025,18(5):565-579,15.基金项目
国家重点研发计划(2021YFC2501701、2021YFC2501703) （2021YFC2501701、2021YFC2501703）
江西省卫生健康委科技计划(202003018) （202003018）
江西省医学领先学科建设项目[老年医学(骨质疏松)] （骨质疏松）
北京协和医院中央高水平医院临床科研专项(揭榜挂帅重大攻关计划2022-PUMCH-D-006) （揭榜挂帅重大攻关计划2022-PUMCH-D-006）
