The role of the gluteofemoral adipose tissue in cerebrovascular disease risk: evidence from a mendelian randomization and mediation analysis
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Le résumé fourni par la source
Objective: To explore causal associations between BMI-independent body fat distribution profiles and cerebrovascular disease risk, and to investigate potential mediators underlying these associations. Methods: Leveraging data from genome wide association studies of BMI-independent gluteofemoral (GFAT), abdominal subcutaneous (ASAT), and visceral (VAT) adipose tissue volumes in UK Biobank, we selected variants associated with each trait, and performed univariable and multivariable mendelian randomization (MR) analyses on ischemic stroke and subtypes (large artery (LAS), cardioembolic (CES), small vessel (SVS)). We used coronary artery disease (CAD), carotid intima media thickness (cIMT), and an MRI-confirmed lacunar stroke as positive controls. For significant associations, we explored the mediatory role of four possible mediator categories in mediation MR analyses. Results: Higher genetically proxied, BMI-independent GFAT volume was associated with decreased risk of ischemic stroke (FDR-p=0.0084), LAS (FDR-p=0.019), SVS (FDR-p<0.001), CAD (FDR-p<0.001), MRI-confirmed lacunar stroke (FDR-p=0.0053), and lower mean cIMT (FDR-p=0.0023), but not CES (FDR-p=0.749). Associations were largely consistent in pleiotropy- and sample structure-robust analyses. No association was observed between genetically proxied ASAT or VAT volumes and ischemic stroke/subtypes risk. In multivariable MR analyses, GFAT showed the most consistent independent association with ischemic stroke, LAS, and SVS. Common vascular risk factors were the predominant mediators in the GFAT-cerebrovascular disease axis, while adipose-tissue-specific adiponectin and leptin mediated a proportion of ischemic stroke and CAD risk. Interpretation: Genetically proxied, BMI-independent higher GFAT volume is associated with reduced cerebrovascular disease risk. Although this is largely mediated by common vascular risk factor modification, targeting adipose-tissue specific pathways may provide additional cardiovascular benefit.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- The role of the gluteofemoral adipose tissue in cerebrovascular disease risk: evidence from a mendelian randomization and mediation analysis
- Date Crossref
- 09/08/2024
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Medical University of South Carolina Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
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Broad Institute Program in Medical and Population Genetics pays non établi dans la noticeOrganisation à but non lucratif
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Institut für Schlaganfall- und Demenzforschung pays non établi dans la noticeUniversité ou école supérieure
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Ludwig-Maximilians-Universität München pays non établi dans la noticeUniversité ou école supérieure
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Brigham and Women's Hospital Department of Neurology pays non établi dans la noticeÉtablissement de santé
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Massachusetts General Hospital Center for Genomic Medicine pays non établi dans la noticeÉtablissement de santé
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Ludwig-Maximilians-University (LMU) Hospital Institute for Stroke and Dementia Research (ISD) pays non établi dans la noticeUniversité ou école supérieure
Department of Neurology — Medical University of South Carolina, Program in Medical and Population Genetics — Broad Institute et Institut für Schlaganfall- und Demenzforschung, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.