TY - JOUR
T1 - GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
AU - MEGASTROKE Consortium
AU - Franceschini, Nora
AU - Giambartolomei, Claudia
AU - de Vries, Paul S.
AU - Finan, Chris
AU - Bis, Joshua C.
AU - Huntley, Rachael P.
AU - Lovering, Ruth C.
AU - Tajuddin, Salman M.
AU - Winkler, Thomas W.
AU - Graff, Misa
AU - Kavousi, Maryam
AU - Dale, Caroline
AU - Smith, Albert V.
AU - Hofer, Edith
AU - van Leeuwen, Elisabeth M.
AU - Nolte, Ilja M.
AU - Lu, Lingyi
AU - Scholz, Markus
AU - Sargurupremraj, Muralidharan
AU - Pitkänen, Niina
AU - Franzén, Oscar
AU - Joshi, Peter K.
AU - Noordam, Raymond
AU - Marioni, Riccardo E.
AU - Hwang, Shih Jen
AU - Musani, Solomon K.
AU - Schminke, Ulf
AU - Palmas, Walter
AU - Isaacs, Aaron
AU - Correa, Adolfo
AU - Zonderman, Alan B.
AU - Hofman, Albert
AU - Teumer, Alexander
AU - Cox, Amanda J.
AU - Uitterlinden, André G.
AU - Wong, Andrew
AU - Smit, Andries J.
AU - Newman, Anne B.
AU - Britton, Annie
AU - Ruusalepp, Arno
AU - Sennblad, Bengt
AU - Hedblad, Bo
AU - Pasaniuc, Bogdan
AU - Penninx, Brenda W.
AU - Langefeld, Carl D.
AU - Wassel, Christina L.
AU - Tzourio, Christophe
AU - Fava, Cristiano
AU - Baldassarre, Damiano
AU - Woo, Daniel
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85057617727
U2 - 10.1038/s41467-018-07340-5
DO - 10.1038/s41467-018-07340-5
M3 - Article
C2 - 30510157
AN - SCOPUS:85057617727
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5141
ER -