Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities
Idioma
EN
Article de revue
Este ítem está publicado en
Nature Communications. 2022-08-03, vol. 13, n° 1
Resumen en inglés
Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending ...Leer más >
Aortic dimensions and distensibility are key risk factors for aortic aneurysms and dissections, as well as for other cardiovascular and cerebrovascular diseases. We present genome-wide associations of ascending and descending aortic distensibility and area derived from cardiac magnetic resonance imaging (MRI) data of up to 32,590 Caucasian individuals in UK Biobank. We identify 102 loci (including 27 novel associations) tagging genes related to cardiovascular development, extracellular matrix production, smooth muscle cell contraction and heritable aortic diseases. Functional analyses highlight four signalling pathways associated with aortic distensibility (TGF-beta, IGF, VEGF and PDGF). We identify distinct sex-specific associations with aortic traits. We develop co-expression networks associated with aortic traits and apply phenome-wide Mendelian randomization (MR-PheWAS), generating evidence for a causal role for aortic distensibility in development of aortic aneurysms. Multivariable MR suggests a causal relationship between aortic distensibility and cerebral white matter hyperintensities, mechanistically linking aortic traits and brain small vessel disease.< Leer menos
Proyecto europeo
Study on Environmental and GenomeWide predictors of early structural brain Alterations in Young students
Common mechanisms and pathways in Stroke and Alzheimer's disease.
PREvention of STroke in Intracerebral haemorrhaGE survivors with Atrial Fibrillation
Common mechanisms and pathways in Stroke and Alzheimer's disease.
PREvention of STroke in Intracerebral haemorrhaGE survivors with Atrial Fibrillation
Proyecto ANR
Stopping cognitive decline and dementia by fighting covert cerebral small vessel disease
Centros de investigación