心脏结构和功能与髋部骨折疾病风险遗传预测的两样本双向孟德尔随机化研究

Genetic prediction for a causal relationship of cardiac structure and function with the risk of hip fracture:a bidirectional,two-sample Mendelian randomization study

目的通过孟德尔随机化(Mendelian randomization,MR)方法来研究心脏结构和功能是否与髋部骨折有因果关系。方法基于大规模全基因组关联研究(GWAS)汇总数据,主要分析方法是逆方差加权法(IVW),使用加权中位数(WM)和MR-Egger作为补充分析方法对心脏结构和功能与髋部骨折的双向因果关系进行探讨。并进行敏感性分析保证结果的稳定性。结果未发现遗传预测的12种心脏磁共振成像(MRI)表型与髋部骨折间的因果关联。在反向MR分析中,髋部骨折与左室每搏输出量(β=-0.04,95%CI=-0.08~-0.00,P=0.032)、右室舒张末容积(β=-0.03,95%CI=-0.07~0.00,P=0.047)、右室收缩末容积(β=-0.04,95%CI=-0.07~-0.00,P=0.047)存在因果关联,而与其他心脏MRI表型无显著关系。结论缺乏强有力的证据支持心脏结构和功能与髋部骨折的因果关系。反之,从基因层面证明了髋部骨折可增加心脏结构和功能异常的风险。

Objective To study whether there is a causal relationship of cardiac structure and function with hip fracture by Mendelian randomization(MR)method.Methods Based on summary data from the large-scale genome-wide association studies(GWAS),the primary analysis method was inverse variance weighted(IVW)method.Weighted median(WM)and MR-Egger methods were used as supplementary analysis methods to explore the bidirectional causal relationship of heart structure and function with hip fracture.Sensitivity analysis were conducted to test the stability of the results.Results No causal association was found between 12 genetic predisposition to cardiac magnetic resonance imaging(MRI)phenotypes and hip fracture.In reverse MR analysis,there was a causal association of hip fracture with left ventricular stroke volume(β=-0.04,95%CI=-0.08 to-0.00,P=0.032),right ventricular end-diastolic volume(β=-0.03,95%CI=-0.07 to 0.00,P=0.047),right ventricular end-systolic volume(β=-0.04,95%CI=-0.07 to-0.00,P=0.047),rather than other cardiac MRI phenotypes.Conclusions There is lack of a strong evidence to support the causal relationship of cardiac structure and function with hip fracture.In the reverse,hip fracture has been shown at the genetic level to increase the risk of cardiac structural and functional abnormalities.