Yiming Jia , Daoxia Guo , Yi Liu , Lulu Sun , Xinyue Chang , Yu He , Mengyao Shi , Guo-Chong Chen , Yonghong Zhang , Li Hui , Zhengbao Zhu
{"title":"Associations between human blood metabolome and vascular dementia","authors":"Yiming Jia , Daoxia Guo , Yi Liu , Lulu Sun , Xinyue Chang , Yu He , Mengyao Shi , Guo-Chong Chen , Yonghong Zhang , Li Hui , Zhengbao Zhu","doi":"10.1016/j.pnpbp.2024.111150","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>Genetically determined glycoproteins (OR per 1-SD increase, 0.75; 95 % CI, 0.68–0.83, <em>P</em> = 1.08 × 10<sup>−8</sup>) and <em>O</em>-methylascorbate (OR per 1-SD increase, 0.08; 95 % CI, 0.02–0.32; <em>P</em> = 3.74 × 10<sup>−4</sup>) 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; <em>P</em> = 1.39 × 10<sup>−4</sup>) and low-density lipoprotein (LDL) cholesterol (OR per 1-SD increase, 1.94; 95 % CI, 1.48–2.55; <em>P</em> = 1.61 × 10<sup>−6</sup>) 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.</div></div><div><h3>Conclusion</h3><div>Glycoproteins, <em>O</em>-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.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0278584624002185","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.