TY - JOUR
T1 - Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities
AU - Francis, Catherine M.
AU - Futschik, Matthias E.
AU - Huang, Jian
AU - Bai, Wenjia
AU - Sargurupremraj, Muralidharan
AU - Teumer, Alexander
AU - Breteler, Monique M.B.
AU - Petretto, Enrico
AU - Ho, Amanda S.R.
AU - Amouyel, Philippe
AU - Engelter, Stefan T.
AU - Bülow, Robin
AU - Völker, Uwe
AU - Völzke, Henry
AU - Dörr, Marcus
AU - Imtiaz, Mohammed Aslam
AU - Aziz, N. Ahmad
AU - Lohner, Valerie
AU - Ware, James S.
AU - Debette, Stephanie
AU - Elliott, Paul
AU - Dehghan, Abbas
AU - Matthews, Paul M.
PY - 2022/8/3
Y1 - 2022/8/3
N2 - AbstractAortic 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-β, 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.
AB - AbstractAortic 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-β, 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.
U2 - 10.1038/s41467-022-32219-x
DO - 10.1038/s41467-022-32219-x
M3 - Article
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -
