基于两样本孟德尔随机化研究白细胞介素-1及其受体与老年肌少症因果关联

Study on causal relationship between interleukin-1 and its receptors and sarcopenia in the elderly based on two-sample Mendelian randomization

中文关键词: 肌少症  白细胞介素1  全基因组关联研究  孟德尔随机化

英文关键词: sarcopenia  interleukin-1  genome-wide association study  Mendelian randomization

中文摘要:

      目的 运用孟德尔随机化(MR)模型探索白细胞介素-1(IL-1)、白细胞介素-1 受体相关蛋白 2(IL-1Rrp2)与老年肌少症之间潜在的因果关系.方法 基于全基因组关联分析数据,以单核苷酸多态性为工具变量,以 IL-1α、IL-1β 和IL-1Rrp2 为暴露因素,分别以四肢瘦体重、左手握力、右手握力、步速为结局,进行两样本 MR 分析,以逆方差加权法作为主要因果效应分析方法,计算 F 值检验工具变量的稳定性,采用 Cochran's Q 统计量检验工具变量间的异质性,并以加权中位数法、MR-Egger 回归进行敏感性分析.结果 研究主要揭示了 IL-1β 和 IL-1Rrp2 与四肢瘦体重之间存在负向因果关联,其效应大小分别为 βIL-1β=-0.019(95%CIIL-1β:0.964～0.999,PIL-1β=0.003)和 βIL-1Rrp2=-0.020(95%CIIL-1Rrp2:0.969～0.992,PIL-1Rrp2<0.001).然而,IL-1α、IL-1β 和 IL-1Rrp2 与左右手握力以及步速之间没有显著关联.结论 IL-1β、IL-1Rrp2 与四肢瘦体重存在负向因果关联.IL-1 和 IL-1 受体都显示出作为管理老年人肌少症治疗潜在靶标的价值.

英文摘要:

      Objective To explore the potential causal relationships between interleukin-1(IL-1),interleukin-1 receptor type 2(IL-1Rrp2),and sarcopenia in the elderly based on Mendelian randomization(MR)model.Methods Based on genome-wide association study data,this study employed single nucleotide polymorphisms as instrumental variables.IL-1α,IL-1β,and IL-1Rrp2 were set as exposures,and appendicular lean mass index,left-hand grip strength,right-hand grip strength,and walking speed were set as outcomes for two-sample MR analysis.The inverse variance weighted method was used as the main causal effect analysis method.The F-value was calculated to test the stability of the instrumental variable.Cochran's Q statistic was used to test the heterogeneity among instrumental variables,and the weighted median method and MR-Egger regression were used for sensitivity analysis.Results The analysis primarily revealed negative causal association of IL-1β and IL-1Rrp2 with appendicular lean mass,with effect sizes of βIL-1β=-0.019(95%CIIL-1β:0.964--0.999,PIL-1β=0.003)and βIL-1Rrp2=-0.020(95%CIIL-1Rrp2:0.969--0.992,PIL-1Rrp2<0.001),respectively.However,no significant associations were observed between IL-1α,IL-1β,or IL-1Rrp2 and left/right hand grip strength or walking speed.Conclusion The findings indicate that IL-1β and IL-1Rrp2 are negatively causally associated with appendicular lean mass.Both IL-1 and IL-1R show potential value as therapeutic targets for managing sarcopenia in the elderly.