Associations between human blood metabolome and vascular dementia

IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Progress in Neuro-Psychopharmacology & Biological Psychiatry Pub Date : 2024-09-19 DOI:10.1016/j.pnpbp.2024.111150
Yiming Jia , Daoxia Guo , Yi Liu , Lulu Sun , Xinyue Chang , Yu He , Mengyao Shi , Guo-Chong Chen , Yonghong Zhang , Li Hui , Zhengbao Zhu
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Abstract

Background

Effective and specific biomarkers are warranted for the management of vascular dementia. We aimed to systematically screen the human blood metabolome to identify potential mediators of vascular dementia via a two-sample Mendelian randomization (MR) design.

Methods

We selected 93 unique blood metabolites from 3 metabolome genome-wide association studies (GWASs) with a total of 147,827 participants of European ancestry. Summary statistics for vascular dementia originated from a European-descent GWAS dataset released by the FinnGen Study, involving 859 cases and 211,300 controls. We applied the inverse-variance weighted MR method in the main analysis to examine the causal roles of blood metabolites in vascular dementia, followed by several sensitivity analyses for robustness validation.

Results

Genetically determined glycoproteins (OR per 1-SD increase, 0.75; 95 % CI, 0.68–0.83, P = 1.08 × 10−8) and O-methylascorbate (OR per 1-SD increase, 0.08; 95 % CI, 0.02–0.32; P = 3.74 × 10−4) levels had negative associations with the risk of vascular dementia, whereas genetically determined total cholesterol (OR per 1-SD increase, 1.77; 95 % CI, 1.32–2.38; P = 1.39 × 10−4) and low-density lipoprotein (LDL) cholesterol (OR per 1-SD increase, 1.94; 95 % CI, 1.48–2.55; P = 1.61 × 10−6) levels had positive associations with the risk of vascular dementia. MR-Egger regression suggested no directional pleiotropy for the identified associations, and sensitivity analyses with different MR models further confirmed these findings.

Conclusion

Glycoproteins, O-methylascorbate, total cholesterol, and LDL cholesterol might be promising blood markers of vascular dementia, which may provide novel insights into the prevention of vascular dementia. Further studies are warranted to replicate our findings and elucidate the potential mechanistic pathways.
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人类血液代谢组与血管性痴呆之间的关系
背景:血管性痴呆症的治疗需要有效而特异的生物标志物。我们旨在通过双样本孟德尔随机化(MR)设计系统地筛选人类血液代谢组,以确定血管性痴呆的潜在介导因素:我们从3项代谢组全基因组关联研究(GWAS)中选取了93种独特的血液代谢物,共有147827名欧洲血统的参与者参与了研究。血管性痴呆的汇总统计数据来自芬兰基因研究(FinnGen Study)发布的欧洲血统 GWAS 数据集,其中包括 859 例病例和 211,300 例对照。我们在主要分析中采用了逆方差加权MR方法来研究血液代谢物在血管性痴呆中的因果作用,随后又进行了几项敏感性分析以验证其稳健性:基因决定的糖蛋白(每增加 1-SD OR,0.75;95 % CI,0.68-0.83,P = 1.08 × 10-8)和 O-甲基抗坏血酸(每增加 1-SD OR,0.08;95 % CI,0.02-0.32;P = 3.74 × 10-4)水平与血管性痴呆风险呈负相关,而基因决定的总胆固醇(每增加 1-SD OR,1.77;95 % CI,1.32-2.38;P = 1.39 × 10-4)和低密度脂蛋白(LDL)胆固醇(OR 每增加 1-SD,1.94;95 % CI,1.48-2.55;P = 1.61 × 10-6)水平与血管性痴呆风险呈正相关。MR-Egger回归表明,已确定的关联不存在方向性多重效应,使用不同MR模型进行的敏感性分析进一步证实了这些发现:结论:糖蛋白、O-甲基抗坏血酸、总胆固醇和低密度脂蛋白胆固醇可能是血管性痴呆有希望的血液标志物,可为预防血管性痴呆提供新的见解。我们有必要开展进一步研究,以复制我们的发现并阐明潜在的机理途径。
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来源期刊
CiteScore
12.00
自引率
1.80%
发文量
153
审稿时长
56 days
期刊介绍: Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject. Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.
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