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K.A. Seldenrijk (Kees),
A.C. Morrison (Alanna),
A. Hamsten (Anders),
B.M. Psaty (Bruce),
C.M. van Duijn (Cornelia),
D.A. Lawlor (Debbie),
Mook-Kanamori, D.O. (Dennis O.),
D.W. Bowden (Donald),
H. Schmidt (Helena),
Wilson, J.F. (James F.),
J.F. Wilson (James),
J.I. Rotter (Jerome I.),
J.M. Wardlaw (J.),
J. Deanfield (John),
Halcox, J. (Julian),
Lyytikäinen, L.-P. (Leo-Pekka),
M. Loeffler (Markus),
M.K. Evans (Michele),
S. Debette (Stéphanie),
S.E. Humphries (Steve),
U. Völker (Uwe),
V. Gudnason (Vilmundur),
A. Hingorani (Aroon),
J.L.M. Björkegren (Johan L.M.),
J.P. Casas (Juan),
C.J. Ódonnell (Christopher)
and
R.W. Morris (Richard)
2018-12-01
GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
Publication
Publication
Nature Communications , Volume 9 - Issue 1
Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Additional Metadata | |
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Persistent URL | doi.org/10.1038/s41467-018-07340-5, hdl.handle.net/1765/112872 |
Journal | Nature Communications |
Grant | This work was funded by the European Commission 7th Framework Programme; grant id fp7/601456 - Exploitation of genomic variants affecting coronary artery disease and stroke risk for therapeutic intervention (CVGENES-AT-TARGET) |
Organisation | Department of Epidemiology |
Citation |
Franceschini, N., Giambartolomei, C. (Claudia), de Vries, P., Finan, C., Bis, J., Huntley, R.P. (Rachael P.), … Morris, R. (2018). GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. Nature Communications, 9(1). doi:10.1038/s41467-018-07340-5 |