背景:尿石症患者容易发生骨质疏松症(OP)是不争的事实,但其具体关联机制尚不清楚。以前的研究集中在环境因素的调解,如饮食;然而,尿石症本身诱发OP的潜力仍不确定。
方法:在本研究中,我们使用来自日本BioBank的数据(6,638例尿石症和7,788例OP病例)来调查尿石症和OP之间的直接因果关系和机制,应用孟德尔随机化(MR),遗传相关分析,共同定位,和路径分析。我们选择了10种遗传变异作为尿石症的工具变量(IVs)。
结果:结果显示遗传预测的尿石症与OP之间存在正相关,在四个模型中调整OP相关因素后,显著的直接效应持续存在。反向分析表明,遗传预测的OP对尿石症没有显着因果关系。虽然遗传相关分析和共定位没有找到确凿的证据,中介分析确定eGFR是一个重要的贡献者。共同风险因素分析揭示了心血管因素是两种情况的共同风险。生物分析暗示细胞因子,新陈代谢,钙信号通路可能连接尿石症和OP,BCAS3DGKH,TBX2和TBX2-AS1被鉴定为潜在的致病基因。
结论:结论:这项研究建立了尿石症和OP之间的直接因果关系,独立于环境因素。不管生活方式如何,尿石症患者应对OP的风险保持警惕,并考虑定期进行OP筛查。尿石症合并OP及相关药物的生物学机制仍需进一步探讨。
BACKGROUND: It is an indisputable fact that patients with urolithiasis are prone to osteoporosis (OP), but the specific mechanism of their association is unclear. Previous studies have focused on the mediation of environmental factors such as diet; however, the potential of urolithiasis itself to induce OP remains uncertain.
METHODS: In this study, we used data from the Japan BioBank (6,638 urolithiasis and 7,788 OP cases) to investigate the direct causal relationship and mechanism between urolithiasis and OP, applying Mendelian randomization (MR), genetic correlation analysis, colocalization, and pathway analysis. We selected ten genetic variants as instrumental variables (IVs) for urolithiasis.
RESULTS: The results showed a positive association between genetically predicted urolithiasis and OP, with significant direct effects persisting after adjusting for OP-associated factors in four models. Reverse analysis revealed no significant causal effect of genetically predicted OP on urolithiasis. While genetic correlation analysis and colocalization did not find conclusive evidence, mediation analysis identified eGFR as a significant contributor. Co-risk factor analysis unveiled cardiovascular elements as common risks for both conditions. Bioanalysis implicates cytokine, metabolic, and calcium signaling pathways may bridge urolithiasis and OP, with BCAS3, DGKH, TBX2, and TBX2-AS1 identified as potential causal genes.
CONCLUSIONS: In conclusion, the study establishes a direct causal link between urolithiasis and OP, independent of environmental factors. Regardless of lifestyle, urolithiasis patients should remain vigilant about the risk of OP and consider regular OP screening. The biological mechanism of urolithiasis combined with OP and related drugs still needs to be further explored.