DataSheet_2_Causal Effect of Blood Pressure on Bone Mineral Density and Fracture: A Mendelian Randomization Study.xlsx

BackgroundHypertension may have some association with osteoporosis. This Mendelian randomization (MR) study aimed to explore the causal effect of blood pressure (BP) on bone mineral density (BMD), fall, and fracture.MethodsWe used the genome-wide association study (GWAS) summary data among 330,956 European-descent individuals to identify 107 single-nucleotide polymorphisms (SNPs) as the instrumental variables of BP. MR analyses of these instruments were performed on 53,236 European individuals for the association with forearm BMD (FA-BMD), femoral neck BMD (FN-BMD), and lumbar spine BMD (LS-BMD); 451,179 European individuals for fall susceptibility; and up to 1.2 million individuals from European descent for fracture. Conventional inverse variance weighted (IVW) method was adopted to obtain the causal estimates of BP on different outcomes, while weighted median, MR-egger, and MR pleiotropy residual sum and outlier (MR-PRESSO) test were used for sensitivity analyses.ResultsGenetically high pulse pressure (PP) could significantly improve FA-BMD (beta-estimate: 0.038, 95% confidence interval [CI]: 0.013 to 0.063, SE:0.013, P-value=0.0032 (95% CI: 0.013 to 0.063). This positive finding was also confirmed by weighted-median analysis (beta-estimate: 0.034, 95% CI: 0.000 to 0.067, SE:0.017, P-value=0.046) and MR-Egger analysis (beta-estimate: 0.117, 95% CI: 0.026 to 0.208, SE:0.046, P-value=0.011). However, there was no remarkable MR association between BP and other outcomes (i.e., FN-BMD, LS-BMD, fall, and fracture).ConclusionsOur findings reveal a potentially causal relationship between high PP and improved FA-BMD, which may provide new sights for the treatment of osteoporosis.

背景：高血压可能与骨质疏松症存在一定的关联。本研究旨在通过孟德尔随机化（MR）方法，探讨血压（BP）对骨矿物质密度（BMD）、跌倒和骨折的因果效应。方法：本研究利用来自330,956名欧洲裔个体的全基因组关联研究（GWAS）汇总数据，确定了107个单核苷酸多态性（SNPs）作为血压的 instrumental variables。对53,236名欧洲裔个体进行MR分析，以探讨这些变量与尺骨远端BMD（FA-BMD）、股骨颈BMD（FN-BMD）和腰椎BMD（LS-BMD）的相关性；对451,179名欧洲裔个体进行跌倒易感性分析；对多达120万欧洲裔个体进行骨折分析。采用传统的逆方差加权（IVW）方法，对血压对不同结局的因果效应进行估计，同时使用加权中位数、Egger MR检验以及多效性残留和异常值（MR-PRESSO）检验进行敏感性分析。结果：遗传学上高脉压（PP）与FA-BMD显著相关（β估计值：0.038，95%置信区间[CI]：0.013至0.063，标准误：0.013，P值=0.0032，95% CI：0.013至0.063）。这一积极发现亦得到加权中位数分析（β估计值：0.034，95% CI：0.000至0.067，标准误：0.017，P值=0.046）和Egger MR检验（β估计值：0.117，95% CI：0.026至0.208，标准误：0.046，P值=0.011）的证实。然而，血压与其他结局（即FN-BMD、LS-BMD、跌倒和骨折）之间未见显著的MR关联。结论：本研究揭示了高PP与FA-BMD之间可能存在的因果联系，这或许为骨质疏松症的治疗提供了新的视角。