Department of Radiology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), No. 19, Xihua St., Xiuying Dis., Haikou, 570311, Hainan, People's Republic of China.
Department of Ultrasound, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), No. 19, Xihua St., Xiuying Dis., Haikou, 570311, Hainan, People's Republic of China.
Sci Rep. 2024 Sep 19;14(1):21862. doi: 10.1038/s41598-024-71881-7.
Previous findings have reported the association between frailty and chronic kidney disease. However, the causality remains ambiguous. This study aimed to determine whether frailty index is causally associated with chronic kidney disease. We obtained the frailty genome-wide association study (GWAS) data and chronic kidney disease GWAS data from the FinnGen R5 (total n = 216,743; case = 3902, control = 212,841) as the exposure and outcome, respectively. A two-sample Mendelian randomization (MR) analysis was primarily conducted using the inverse-variance weighted (IVW), weighted median and MR-Egger regression analyses. Multivariable MR analysis (MVMR) was conducted for additional adjustment. In the two-sample Mendelian randomization analyses, a total of 14 single nucleotide polymorphisms (SNPs) were recognized as effective instrumental variables. The IVW method showed evidence to support a causal association between frailty index and chronic kidney disease (beta = 1.270; 95% CI 0.608 to 1.931; P < 0.001). MR-Egger revealed a causal association between frailty index and chronic kidney disease (beta = 3.612; 95% CI 0.805 to 6.419; P = 0.027). MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = - 0.053; P = 0.119). The weighted median approach and weighted mode method also demonstrated a causal association between frailty index and chronic kidney disease (beta = 1.148; 95% CI 0.278 to 2.019; P = 0.011; beta = 2.194; 95% CI 0.598 to 3.790; P = 0.018). Cochran's Q test and the funnel plot indicated no directional pleiotropy. MVMR analysis revealed that the causal association between frailty index and chronic kidney disease remained after adjusting for potential confounders, body-mass index, inflammatory bowel disease, waist-hip ratio, and C-reactive protein. Our study provides evidence of causal association between frailty and chronic kidney disease from genetic perspectives.
先前的研究报告了虚弱与慢性肾脏病之间的关联。然而，其因果关系仍不明确。本研究旨在确定虚弱指数是否与慢性肾脏病存在因果关系。我们分别从 FinnGen R5（总人数为 216743 人；病例=3902 例，对照=212841 例）中获得了虚弱全基因组关联研究（GWAS）数据和慢性肾脏病 GWAS 数据作为暴露和结局。主要采用逆方差加权（IVW）、加权中位数和 MR-Egger 回归分析进行两样本 Mendelian 随机化（MR）分析。多变量 Mendelian 随机化分析（MVMR）用于额外调整。在两样本 Mendelian 随机化分析中，共识别出 14 个单核苷酸多态性（SNP）作为有效工具变量。IVW 方法表明，虚弱指数与慢性肾脏病之间存在因果关系（β=1.270；95%CI 0.608 至 1.931；P<0.001）。MR-Egger 表明虚弱指数与慢性肾脏病之间存在因果关系（β=3.612；95%CI 0.805 至 6.419；P=0.027）。MR-Egger 回归表明，定向异质性不太可能影响结果（截距=-0.053；P=0.119）。加权中位数法和加权众数法也表明，虚弱指数与慢性肾脏病之间存在因果关系（β=1.148；95%CI 0.278 至 2.019；P=0.011；β=2.194；95%CI 0.598 至 3.790；P=0.018）。Cochran's Q 检验和漏斗图表明不存在定向异质性。MVMR 分析表明，在调整潜在混杂因素（体重指数、炎症性肠病、腰臀比和 C 反应蛋白）后，虚弱指数与慢性肾脏病之间的因果关系仍然存在。本研究从遗传角度提供了虚弱与慢性肾脏病之间存在因果关系的证据。
