骨质疏松症与牙周炎的因果关系:一项两样本孟德尔随机化研究

The causal association between osteoporosis and periodontitis:A two-sample Mendelian randomization

目的:采用孟德尔随机化研究探索骨质疏松症与牙周炎是否存在因果关系。方法:从两个全基因组关联研究(GWAS)数据库(GEFOS,欧洲人,n = 142 487;BBJ,东亚人,n = 212 453)中筛选与骨质疏松症(暴露因素)密切相关且相互独立的单核苷酸多态性(SNP)位点。从另外两个GWAS数据库(GLIDE,欧洲人,n = 45 563;BBJ,东亚人,n = 212 453)获取牙周炎(结局事件)的SNP位点,选出与暴露因素对应的SNP作为工具变量。采用逆方差加权(IVW)、MR-Egger回归和加权中位数等方法进行两样本孟德尔随机化分析,以OR值评价骨质疏松症与牙周炎的因果关联。结果:从欧洲人群和东亚人群中筛出207和7个SNP。逆方差加权法不支持骨质疏松症与牙周炎存在因果关系(欧洲:OR = 0.964,P = 0.281;东亚:OR = 0.892,P = 0.090)。MR-Egger回归截距不为0,表明无遗传多效性(截距= 0.000 3,P = 0.909)。"leave-one-out"分析未发现特异性SNP。结论:针对欧洲和东亚人群的孟德尔随机化研究,不支持骨质疏松症与牙周炎存在因果关系。

Objective To explore the causal relationship between osteoporosis and periodontitis with Mendelian randomization(MR)analysis.Methods Mutually independent SNPs associated with osteoporosis(exposure)were screened out from two Genome-wide association study(GWAS)databases(GEFOS,European,n=142487;BBJ,East Asian,n=212453).The SNP data on periodontitis(outcome)were obtained from another two GWAS databases and relevant SNPs corresponding to the exposure were selected as instrumental variables.Two-sample MR analysis was conducted with methods of inverse variance weighted(IVW),MR-Egger regression and weighted median.The causal association between osteoporosis and periodontitis was estimated with odds ratios.Results Totally 207 and 7 SNPs were screened out from European and East Asian populations,respectively.IVW did not support a causal relationship between osteoporosis and periodontitis(European:odds ratio=0.964,P=0.281;East Asian:odds ratio=0.892,P=0.090).The intercept of MR-Egger regression was unequal to zero,suggesting there was no genetic pleiotropy(intercept=0.0003,P=0.909).Specific SNP was not found with leave-one-out analysis.Conclusion MR study does not support a causal association between osteoporosis and periodontitis in European and East Asian populations.