利用孟德尔随机化探讨肥胖与骨密度的因果关系及作用机制  

Using Mendelian randomization to explore the causal association and mechanisms between obesity and bone mineral density

作　　者：贺麟 黄德琴 申鹏悦 瞿阳 朱经纬 张本[1] HE Lin;HUANG De-qin;SHEN Peng-yue;QU Yang;ZHU Jing-wei;ZHANG Ben(West China School of Public Health and West China Fourth Hospital,Sichuan University,Chengdu,Sichuan 610041,China)

机构地区：[1]四川大学华西公共卫生学院/四川大学华西第四医院,四川成都610041

出　　处：《现代预防医学》2024年第4期602-606,共5页Modern Preventive Medicine

摘　　要：目的 采用孟德尔随机化(Mendelian randomization, MR)研究肥胖与骨密度的因果关系和作用机制。方法 利用身体质量指数(body mass index, BMI)、体脂百分比和全身骨密度的全基因组关联研究(genome-wide association study, GWAS)数据库进行单变量两样本MR分析,探究肥胖与骨密度之间的因果关系,并应用多变量MR方法校正瘦体质和体重等变量,探究肥胖与骨密度之间的作用机制。结果 单变量MR结果显示,BMI对全身骨密度呈现显著的保护作用(β=0.06,95%CI:0.03~0.09)且不存在性别特异性,而体脂百分比与全身骨密度之间没有显著因果效应(β=-0.01,P=0.13)。经多变量MR校正瘦体质(β=0.04,P=0.06)和体重(β=0.03,P=0.48)后,BMI对全身骨密度的保护作用消失。而体脂百分比在校正瘦体质(β=-0.02,95%CI:-0.03~0.00)和体重(β=-0.05,95%CI:-0.07~-0.02)后,均观察到了显著的负向因果效应。结论 肥胖主要通过体重和瘦体质等机械负荷相关指标发挥保护作用,而脂肪本身对骨密度呈现破坏作用。Objective To investigate the causal relationship and mechanisms between obesity and bone mineral density using Mendelian randomization(MR).Methods Using genome-wide association study(GWAS)datasets of body mass index(BMI),body fat percentage,and total body bone mineral density,univariate two-sample MR analysis was conducted to explore the causal relationship between obesity and bone mineral density.A multivariate MR method was also employed to adjust for variables such as lean mass and body weight to investigate the underlying mechanisms.Results Univariate MR analysis showed a significant protective effect of BMI on total body bone mineral density(β=0.06,95%CI:0.03-0.09)with consistent results across sex-specific studies,while no significant causal effect was found between body fat percentage and total body bone mineral density(β=-0.01,P=0.13).After adjusting for lean mass(β=0.04,P=0.06)and weight(β=0.03,P=0.48)using multivariate MR,the protective effect of BMI on total body bone mineral density disappeared.In contrast,a significant negative causal effect was observed between body fat percentage and total body bone mineral density after adjusting for lean mass(β=-0.02,95%CI:-0.03-0.00)and weight(β=-0.05,95%CI:-0.07--0.02).Conclusion Obesity primarily exerts a protective effect on bone mineral density through mechanically-related indicators such as weight and lean mass,while body fat itself has a detrimental effect on bone mineral density.

关 键 词：孟德尔随机化 身体质量指数 体脂百分比 全身骨密度 

分 类 号：R195[医药卫生—卫生统计学]