Department of General Practice, Zhongshan Hospital of Fudan University, Shanghai 200032, China.
The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310003, Zhejiang, China.
Exp Gerontol. 2024 Oct 1;195:112545. doi: 10.1016/j.exger.2024.112545. Epub 2024 Aug 18.
The association between frailty and sex hormone-binding globulin (SHBG) or insulin-like growth factor-1(IGF-1) levels demonstrates sex differences with inconsistent conclusions. This study aims to explore the causal relationship between frailty and SHBG or IGF-1 levels through bidirectional Mendelian randomization (MR).
We conducted two-sample bidirectional sex-stratified MR analyses using summary-level data from genome-wide association studies (GWASs) to examine the causal relationship between frailty and IGF-1 or SHBG levels, as measured by frailty index (FI) and frailty phenotype (FP). We use the random-effects inverse-variance weighted (IVW), weighted median, MR-Egger, MR-Egger intercept, and leave-one-out approaches.
The relationship between frailty and SHBG or IGF-1 levels is inversely related, with a significant decrease in SHBG levels in females. Specifically, SHBG levels significantly decrease with FI (β = -5.49; 95 % CI: -9.67 to -1.32; FDR = 0.02) and more pronounced with FP (β = -10.14; 95 % CI: -16.16 to -4.13; FDR = 0.01), as determined by the IVW approach. However, reverse analysis shows no significant effect of IGF-1 or SHBG levels on either FI or FP (p > 0.05).
Our study indicates a negative correlation between frailty and the levels of SHBG and IGF-1. It is suggested that further research is required to establish cut-off values for SHBG and IGF-1 levels in the frailty population. This is particularly important for females at higher risk, such as those undergoing menopause, to enable comprehensive assessment and early prevention efforts. While the findings imply that reduced IGF-1 and SHBG levels may not directly contribute to frailty, it is important not to overlook the underlying mechanisms through which they may indirectly influence frailty.
虚弱与性激素结合球蛋白（SHBG）或胰岛素样生长因子-1（IGF-1）水平之间的关联表现出性别差异，结论不一致。本研究旨在通过双向孟德尔随机化（MR）探索虚弱与 SHBG 或 IGF-1 水平之间的因果关系。
我们使用来自全基因组关联研究（GWAS）的汇总水平数据进行两样本双向性别分层 MR 分析，以检查虚弱与 IGF-1 或 SHBG 水平之间的因果关系，这些水平由虚弱指数（FI）和虚弱表型（FP）测量。我们使用随机效应逆方差加权（IVW）、加权中位数、MR-Egger、MR-Egger 截距和逐一剔除方法。
虚弱与 SHBG 或 IGF-1 水平之间的关系呈负相关，女性的 SHBG 水平显著降低。具体而言，SHBG 水平与 FI 呈显著负相关（β=-5.49；95%CI：-9.67 至-1.32；FDR=0.02），与 FP 更显著相关（β=-10.14；95%CI：-16.16 至-4.13；FDR=0.01），根据 IVW 方法。然而，反向分析显示 IGF-1 或 SHBG 水平对 FI 或 FP 没有显著影响（p>0.05）。
本研究表明虚弱与 SHBG 和 IGF-1 水平之间呈负相关。建议进一步研究确定虚弱人群中 SHBG 和 IGF-1 水平的截断值。对于处于更高风险的女性（例如，正在经历更年期的女性），这一点尤为重要，以便进行全面评估和早期预防工作。虽然研究结果表明，IGF-1 和 SHBG 水平的降低可能不会直接导致虚弱，但不应忽视它们可能通过间接途径影响虚弱的潜在机制。
