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动脉僵硬度指数与年龄相关疾病之间的关联:一项孟德尔随机化研究。

Association Between Arterial Stiffness Index and Age-Related Diseases: A Mendelian Randomization Study.

作者信息

Yu Xiaojie, Cao Yang, Li Xinyi, Liang Qingchun, Dong Xiaodan, Liang Bing

机构信息

Department of Anesthesiology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China.

Department of Anesthesiology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.

出版信息

Rejuvenation Res. 2025 Feb;28(1):9-16. doi: 10.1089/rej.2024.0041. Epub 2024 Oct 7.

Abstract

Arterial stiffness is an emerging indicator of cardiovascular risk, but its causal relationship with a variety of age-related diseases is unclear. The objective is to assess the causal relationship between arterial stiffness index (ASI) and age-related diseases by Mendelian randomization (MR) analysis. We obtained instrumental variables associated with age-related diseases from genome-wide association studies (GWAS) of 484,598 European individuals, and data for ASI were obtained from the UK Biobank GWAS of 127,127 participants. We used the inverse variance-weighted as the primary analysis method. In addition, several sensitivity analyses including MR-Egger, weighted-median (WM), Mendelian randomization pleiotropy residual sum and outlier, and Cochran's Q test were performed to test the robustness of the results. Reverse MR analysis was also performed to assess reverse causal relationships between age-related diseases and ASI. We verified the causal relationship between eight age-related diseases and ASI, of which cardiovascular disease ( = 0.19), gallbladder disease ( = 0.85), liver, biliary, or pancreas problem ( = 1.02), hypertension ( = 0.19), joint disorder ( = 0.53), and esophageal disorder ( = 2.10) elevated ASI. In contrast, hyperthyroidism or thyrotoxicosis ( = -2.17) and bowel problems ( = -1.83) may reduce ASI. This MR analysis reveals causal relationships between ASI and several age-related diseases. ASI is expected to be a potential indicator of health conditions for older populations.

摘要

动脉僵硬度是心血管风险的一个新出现的指标,但其与多种年龄相关疾病的因果关系尚不清楚。目的是通过孟德尔随机化(MR)分析评估动脉僵硬度指数(ASI)与年龄相关疾病之间的因果关系。我们从484,598名欧洲个体的全基因组关联研究(GWAS)中获得了与年龄相关疾病相关的工具变量,而ASI的数据则来自127,127名参与者的英国生物银行GWAS。我们使用逆方差加权作为主要分析方法。此外,还进行了多项敏感性分析,包括MR-Egger、加权中位数(WM)、孟德尔随机化多效性残差和异常值分析以及 Cochr an's Q检验,以检验结果的稳健性。还进行了反向MR分析,以评估年龄相关疾病与ASI之间的反向因果关系。我们验证了八种年龄相关疾病与ASI之间的因果关系,其中心血管疾病( = 0.19)、胆囊疾病( = 0.85)、肝脏、胆道或胰腺问题( = 1.02)、高血压( = 0.19)、关节疾病( = 0.53)和食管疾病( = 2.10)会升高ASI。相比之下,甲状腺功能亢进或甲状腺毒症( = -2.17)和肠道问题( = -1.83)可能会降低ASI。这项MR分析揭示了ASI与几种年龄相关疾病之间的因果关系。ASI有望成为老年人群健康状况的潜在指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/488b/11844224/cd01dfb839f7/rej.2024.0041_figure1.jpg

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