Genome-wide and phenome-wide studies provided insights into brain glymphatic system function and its clinical associations

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-01-17 DOI:10.1126/sciadv.adr4606

Lusen Ran, Yuanyuan Fang, Chang Cheng, Yuqin He, Zhonghe Shao, Yifan Kong, Hao Huang, Shabei Xu, Xiang Luo, Wei Wang, Xingjie Hao, Minghuan Wang

{"title":"Genome-wide and phenome-wide studies provided insights into brain glymphatic system function and its clinical associations","authors":"Lusen Ran, Yuanyuan Fang, Chang Cheng, Yuqin He, Zhonghe Shao, Yifan Kong, Hao Huang, Shabei Xu, Xiang Luo, Wei Wang, Xingjie Hao, Minghuan Wang","doi":"10.1126/sciadv.adr4606","DOIUrl":null,"url":null,"abstract":"<div >We applied an MRI technique diffusion tensor imaging along the perivascular space (DTI-ALPS) for assessing glymphatic system (GS) in a genome-wide association study (GWAS) and phenome-wide association study (PheWAS) of 40,486 European individuals. Exploratory analysis revealed 17 genetic loci significantly associating with the regional DTI-ALPS index. We found 58 genes, including <i>SPPL2C</i> and <i>EFCAB5</i>, which prioritized in the DTI-ALPS index subtypes and associated with neurodegenerative diseases. PheWAS of 241 traits suggested that body mass index and blood pressure phenotypes closely related to GS function. Moreover, we detected disrupted GS function in 44 of 625 predefined disease conditions. Notably, Mendelian randomization and mediation analysis indicated that lower DTI-ALPS index was a risk factor for ischemic stroke (odds ratio = 1.56, <i>P</i> = 0.028) by partly mediating the risk factor of obesity. Results provide insights into the genetic architecture and mechanism for the DIT-ALPS index and highlight its great clinical value, especially in cerebral stroke.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 3","pages":""},"PeriodicalIF":11.7000,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adr4606","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Advances","FirstCategoryId":"103","ListUrlMain":"https://www.science.org/doi/10.1126/sciadv.adr4606","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

We applied an MRI technique diffusion tensor imaging along the perivascular space (DTI-ALPS) for assessing glymphatic system (GS) in a genome-wide association study (GWAS) and phenome-wide association study (PheWAS) of 40,486 European individuals. Exploratory analysis revealed 17 genetic loci significantly associating with the regional DTI-ALPS index. We found 58 genes, including SPPL2C and EFCAB5, which prioritized in the DTI-ALPS index subtypes and associated with neurodegenerative diseases. PheWAS of 241 traits suggested that body mass index and blood pressure phenotypes closely related to GS function. Moreover, we detected disrupted GS function in 44 of 625 predefined disease conditions. Notably, Mendelian randomization and mediation analysis indicated that lower DTI-ALPS index was a risk factor for ischemic stroke (odds ratio = 1.56, P = 0.028) by partly mediating the risk factor of obesity. Results provide insights into the genetic architecture and mechanism for the DIT-ALPS index and highlight its great clinical value, especially in cerebral stroke.

Abstract Image

查看原文本刊更多论文

全基因组和全现象研究提供了对脑淋巴系统功能及其临床关联的见解

我们在40,486名欧洲人的全基因组关联研究（GWAS）和全表型关联研究（PheWAS）中应用MRI技术沿血管周围间隙扩散张量成像（DTI-ALPS）来评估淋巴系统（GS）。探索性分析发现17个遗传位点与区域DTI-ALPS指数显著相关。我们发现了58个基因，包括SPPL2C和EFCAB5，它们优先出现在DTI-ALPS指数亚型中，并与神经退行性疾病相关。241个性状的PheWAS表明体重指数和血压表型与GS功能密切相关。此外，我们在625种预定义疾病条件中的44种中检测到GS功能中断。值得注意的是，孟德尔随机化和中介分析表明，较低的DTI-ALPS指数通过部分介导肥胖的危险因素而成为缺血性卒中的危险因素（优势比= 1.56,P = 0.028）。研究结果揭示了DIT-ALPS指数的遗传结构和机制，并突出了其在脑卒中中的重要临床价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.