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  • GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

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    Author(s)
    Franceschini, Nora
    Giambartolomei, Claudia
    de Vries, Paul S
    Finan, Chris
    Bis, Joshua C
    Huntley, Rachael P
    Lovering, Ruth C
    Tajuddin, Salman M
    Winkler, Thomas W
    Graff, Misa
    Kavousi, Maryam
    Dale, Caroline
    Smith, Albert V
    Hofer, Edith
    van Leeuwen, Elisabeth M
    Nolte, Ilja M
    Lu, Lingyi
    Scholz, Markus
    Sargurupremraj, Muralidharan
    Pitkanen, Niina
    Franzen, Oscar
    Joshi, Peter K
    Noordam, Raymond
    Marioni, Riccardo E
    Hwang, Shih-Jen
    Musani, Solomon K
    Schminke, Ulf
    Palmas, Walter
    Isaacs, Aaron
    Correa, Adolfo
    Zonderman, Alan B
    Hofman, Albert
    Teumer, Alexander
    Cox, Amanda J
    Uitterlinden, Andre G
    Wong, Andrew
    Smit, Andries J
    Newman, Anne B
    Britton, Annie
    Ruusalepp, Arno
    Sennblad, Bengt
    Hedblad, Bo
    Pasaniuc, Bogdan
    Penninx, Brenda W
    Langefeld, Carl D
    Wassel, Christina L
    Tzourio, Christophe
    Fava, Cristiano
    Baldassarre, Damiano
    O'Leary, Daniel H
    Teupser, Daniel
    Kuh, Diana
    Tremoli, Elena
    Mannarino, Elmo
    Grossi, Enzo
    Boerwinkle, Eric
    Schadt, Eric E
    Ingelsson, Erik
    Veglia, Fabrizio
    Rivadeneira, Fernando
    Beutner, Frank
    Chauhan, Ganesh
    Heiss, Gerardo
    Snieder, Harold
    Campbell, Harry
    Voelzke, Henry
    Markus, Hugh S
    Deary, Ian J
    Jukema, J Wouter
    de Graaf, Jacqueline
    Price, Jacqueline
    Pott, Janne
    Hopewell, Jemma C
    Liang, Jingjing
    Thiery, Joachim
    Engmann, Jorgen
    Gertow, Karl
    Rice, Kenneth
    Taylor, Kent D
    Dhana, Klodian
    Kiemeney, Lambertus ALM
    Lind, Lars
    Raffield, Laura M
    Launer, Lenore J
    Holdt, Lesca M
    Doer, Marcus
    Dichgans, Martin
    Traylor, Matthew
    Sitzer, Matthias
    Kumari, Meena
    Kivimaki, Mika
    Nalls, Mike A
    Melander, Olle
    Raitakari, Olli
    Franco, Oscar H
    Rueda-Ochoa, Oscar L
    Roussos, Panos
    Whincup, Peter H
    Amouyel, Philippe
    Giral, Philippe
    Anugu, Pramod
    Wong, Quenna
    Malik, Rainer
    Rauramaa, Rainer
    Burkhardt, Ralph
    Hardy, Rebecca
    Schmidt, Reinhold
    de Mutsert, Renee
    Morris, Richard W
    Strawbridge, Rona J
    Wannamethee, S Goya
    Hagg, Sara
    Shah, Sonia
    McLachlan, Stela
    Trompet, Stella
    Seshadri, Sudha
    Kurl, Sudhir
    Heckbert, Susan R
    Ring, Susan
    Harris, Tamara B
    Lehtimaki, Terho
    Galesloot, Tessel E
    Shah, Tina
    de Faire, Ulf
    Plagnol, Vincent
    Rosamond, Wayne D
    Post, Wendy
    Zhu, Xiaofeng
    Zhang, Xiaoling
    Guo, Xiuqing
    Saba, Yasaman
    Dehghan, Abbas
    Seldenrijk, Adrie
    Morrison, Alanna C
    Hamsten, Anders
    Psaty, Bruce M
    van Duijn, Cornelia M
    Lawlor, Deborah A
    Mook-Kanamori, Dennis O
    Bowden, Donald W
    Schmidt, Helena
    Wilson, James F
    Wilson, James G
    Rotter, Jerome I
    Wardlaw, Joanna M
    Deanfield, John
    Halcox, Julian
    Lyytikainen, Leo-Pekka
    Loeffler, Markus
    Evans, Michele K
    Debette, Stephanie
    Humphries, Steve E
    Voelker, Uwe
    Gudnason, Vilmundur
    Hingorani, Aroon D
    Bjorkegren, Johan LM
    Casas, Juan P
    O'Donnell, Christopher J
    Griffith University Author(s)
    Cox, Amanda J.
    Year published
    2018
    Metadata
    Show full item record
    Abstract
    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 ...
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    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.
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    Journal Title
    Nature Communications
    Volume
    9
    DOI
    https://doi.org/10.1038/s41467-018-07340-5
    Copyright Statement
    © The Author(s) 2018. This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Subject
    Other biomedical and clinical sciences not elsewhere classified
    Cardiovascular medicine and haematology
    Publication URI
    http://hdl.handle.net/10072/382051
    Collection
    • Journal articles

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