학술논문
Circulating Metabolome and White Matter Hyperintensities in Women and Men
Document Type
article
Author
Sliz, Eeva; Shin, Jean; Ahmad, Shahzad; Williams, Dylan M; Frenzel, Stefan; Gauß, Friederike; Harris, Sarah E; Henning, Ann-Kristin; Hernandez, Maria Valdes; Hu, Yi-Han; Jiménez, Beatriz; Sargurupremraj, Muralidharan; Sudre, Carole; Wang, Ruiqi; Wittfeld, Katharina; Yang, Qiong; Wardlaw, Joanna M; Völzke, Henry; Vernooij, Meike W; Schott, Jonathan M; Richards, Marcus; Proitsi, Petroula; Nauck, Matthias; Lewis, Matthew R; Launer, Lenore; Hosten, Norbert; Grabe, Hans J; Ghanbari, Mohsen; Deary, Ian J; Cox, Simon R; Chaturvedi, Nishi; Barnes, Josephine; Rotter, Jerome I; Debette, Stephanie; Ikram, M Arfan; Fornage, Myriam; Paus, Tomas; Seshadri, Sudha; Pausova, Zdenka; Group, for the NeuroCHARGE Working
Source
Circulation. 145(14)
Subject
Language
Abstract
BackgroundWhite matter hyperintensities (WMH), identified on T2-weighted magnetic resonance images of the human brain as areas of enhanced brightness, are a major risk factor of stroke, dementia, and death. There are no large-scale studies testing associations between WMH and circulating metabolites.MethodsWe studied up to 9290 individuals (50.7% female, average age 61 years) from 15 populations of 8 community-based cohorts. WMH volume was quantified from T2-weighted or fluid-attenuated inversion recovery images or as hypointensities on T1-weighted images. Circulating metabolomic measures were assessed with mass spectrometry and nuclear magnetic resonance spectroscopy. Associations between WMH and metabolomic measures were tested by fitting linear regression models in the pooled sample and in sex-stratified and statin treatment-stratified subsamples. Our basic models were adjusted for age, sex, age×sex, and technical covariates, and our fully adjusted models were also adjusted for statin treatment, hypertension, type 2 diabetes, smoking, body mass index, and estimated glomerular filtration rate. Population-specific results were meta-analyzed using the fixed-effect inverse variance-weighted method. Associations with false discovery rate (FDR)-adjusted P values (PFDR)