磷脂酰胆碱与脆弱:孟德尔随机研究和免疫中介

IF 3.5 3区 医学 Q2 GERIATRICS & GERONTOLOGY
Qunhua Han , Suisui Luo , Shunmei Huang , Yunmei Yang , Qin Zhang , Lijun Zhu
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引用次数: 0

摘要

目的脂质代谢在衰老过程中起着重要作用,随着年龄的增长,虚弱的患病率增加。然而,很少有研究采用孟德尔随机化(MR)来调查脂质和虚弱之间的关系。方法采用大规模全基因组关联研究(GWAS)和双向双样本两步MR方法,探讨179种脂质与脆性指数(FI)的因果关系以及免疫细胞的介导作用。主要采用逆方差加权(IVW)方法评价MR结果。异质性和水平多效性通过Cochran’s Q、MR-Egger截距、MR-PRESSO和留一分析进行评估。全现象磁共振(Phe-MR)用于分析与衰弱相关的磷脂酰胆碱物种在疾病中的潜在作用。结果smr分析揭示了PC种与FI之间的因果关系。其中,PC(18:0_20:5)、LPC(18:0_0:0)、LPC(16:0_0:0)、以太-PC (O-16:0_22:5)与FI呈显著正相关,PC(18:1_20 . 2)、PC(16:0_18 . 3)、PC(16:0_20 . 1)、以太-PC (o -16:1_16 . 0)与FI呈显著负相关。反向MR分析表明FI和9个pc之间没有很强的关联。介导分析显示,Sw mem %淋巴细胞部分介导LPC(18:0 ~ 0:0)对FI的影响。Phe-MR分析显示,9种与衰弱相关的pc与多种疾病广泛相关。结论本研究提供了新的证据,支持PC物种与脆弱之间的因果关系,免疫系统在这一途径中发挥重要作用。这些发现为老年人群虚弱干预的潜在目标提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Phosphatidylcholine and frailty: a Mendelian randomization study and immune mediation

Phosphatidylcholine and frailty: a Mendelian randomization study and immune mediation

Objective

Lipid metabolism plays a significant role in the aging process, and the prevalence of frailty increases with advancing age. However, few studies have employed Mendelian randomization (MR) to investigate the associations between lipids and frailty.

Methods

This study utilized large-scale genome-wide association study (GWAS) and a bidirectional two-sample, two-step MR approach to explore the causal associations of 179 lipid species with the frailty index (FI) and the mediating effects of immune cells. The inverse variance weighted (IVW) method was used primarily to evaluate the MR results. Heterogeneity and horizontal pleiotropy were assessed via Cochran’s Q, the MR-Egger intercept, MR-PRESSO and leave-one-out analysis. Phenome-wide MR (Phe-MR) was used to analyse the potential roles of frailty-related phosphatidylcholine species in diseases.

Results

MR analysis revealed a causal relationship between PC species and FI. Specifically, PC (18:0_20:5), LPC (18:0_0:0), LPC (16:0_0:0), and ether-PC (O-16:0_22:5) are positively correlated with the FI, whereas PC(18:1_20:2), PC(16:0_18:3), PC(16:0_20:1), ether-PC (O-18:0_16:1), and ether-PC (O-16:1_16:0) are negatively correlated with the FI. Reverse MR analysis indicated no strong association between the FI and the nine PCs. Mediation analysis revealed that Sw mem %lymphocyte partially mediated the effect of LPC (18:0_0:0) on FI. Phe-MR analysis revealed that nine frailty-related PCs were broadly associated with various diseases.

Conclusion

This study provides novel evidence that supports the causal association between PC species and frailty, with the immune system playing a crucial role in this pathway. These findings offer new insights into potential targets for the intervention of frailty in the elderly population.
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来源期刊
CiteScore
7.30
自引率
5.00%
发文量
198
审稿时长
16 days
期刊介绍: Archives of Gerontology and Geriatrics provides a medium for the publication of papers from the fields of experimental gerontology and clinical and social geriatrics. The principal aim of the journal is to facilitate the exchange of information between specialists in these three fields of gerontological research. Experimental papers dealing with the basic mechanisms of aging at molecular, cellular, tissue or organ levels will be published. Clinical papers will be accepted if they provide sufficiently new information or are of fundamental importance for the knowledge of human aging. Purely descriptive clinical papers will be accepted only if the results permit further interpretation. Papers dealing with anti-aging pharmacological preparations in humans are welcome. Papers on the social aspects of geriatrics will be accepted if they are of general interest regarding the epidemiology of aging and the efficiency and working methods of the social organizations for the health care of the elderly.
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