DataSheet_3_Causal Effect of Blood Pressure on Bone Mineral Density and Fracture: A Mendelian Randomization Study.pdf

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：高血压与骨质疏松症之间可能存在某种关联。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名欧洲血统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）作为血压的工具变量。对这些工具变量的MR分析在53,236名欧洲个体中进行了，以探究与前臂骨矿物质密度（FA-BMD）、股骨颈骨矿物质密度（FN-BMD）和腰椎骨矿物质密度（LS-BMD）的相关性；在451,179名欧洲个体中进行了跌倒易感性的探究；以及从欧洲血统的至120万个体中进行了骨折的研究。采用传统逆方差加权（IVW）方法以获得血压对不同结局的因果估计，同时使用加权中位数、MR-Egger检验以及MR多效性残留和异常值检验（MR-PRESSO）进行敏感性分析。结果：遗传性高脉压（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）。这一积极发现亦由加权中位数分析（β估计值：0.034，95% CI：0.000至0.067，标准误：0.017，P值=0.046）和MR-Egger分析（β估计值：0.117，95% CI：0.026至0.208，标准误：0.046，P值=0.011）所证实。然而，血压与其他结局（即FN-BMD、LS-BMD、跌倒和骨折）之间并未发现显著的MR关联。结论：本研究揭示了高PP与FA-BMD之间的潜在因果关系，这或许为骨质疏松症的治疗提供了新的视角。