GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Franceschini, Nora; Giambartolomei, Claudia; Vries, Paul; Finan, Chris; Bis, Joshua; Huntley, Rachael; Lovering, Ruth; Tajuddin, Salman; Winkler, Thomas; Graff, Misa; Kavousi, Maryam; Dale, Caroline; Smith, Albert; Hofer, Edith; Leeuwen, Elisabeth; Nolte, Ilja; Lu, Lingyi; Scholz, Markus; Sargurupremraj, Muralidharan; Pitkänen, Niina; Franzén, Oscar; Joshi, Peter; Noordam, Raymond; Marioni, Riccardo; Hwang, Shih-Jen; Musani, Solomon; Schminke, Ulf; Palmas, Walter; Isaacs, Aaron; Correa, Adolfo; Zonderman, Alan; Hofman, Albert; Teumer, Alexander; Cox, Amanda; Uitterlinden, André; Wong, Andrew; Smit, Andries; Newman, Anne; Britton, Annie; Ruusalepp, Arno; Sennblad, Bengt; Hedblad, Bo; Pasaniuc, Bogdan; Penninx, Brenda; Langefeld, Carl; Wassel, Christina; Tzourio, Christophe; Fava, Cristiano; Baldassarre, Damiano; O'Leary, Daniel; Teupser, Daniel; Kuh, Diana; Tremoli, Elena; Mannarino, Elmo; Grossi, Enzo; Boerwinkle, Eric; Schadt, Eric; Ingelsson, Erik; Veglia, Fabrizio; Rivadeneira, Fernando; Beutner, Frank; Chauhan, Ganesh; Heiss, Gerardo; Snieder, Harold; Campbell, Harry; Völzke, Henry; Markus, Hugh; Deary, Ian; Jukema, J.; Graaf, Jacqueline; Price, Jacqueline; Pott, Janne; Hopewell, Jemma; Liang, Jingjing; Thiery, Joachim; Engmann, Jorgen; Gertow, Karl; Rice, Kenneth; Taylor, Kent; Dhana, Klodian; Kiemeney, Lambertus; Lind, Lars; Raffield, Laura; Launer, Lenore; Holdt, Lesca; Dörr, Marcus; Dichgans, Martin; Traylor, Matthew; Sitzer, Matthias; Kumari, Meena; Kivimaki, Mika; Nalls, Mike; Melander, Olle; Raitakari, Olli; Franco, Oscar; Rueda-Ochoa, Oscar; Roussos, Panos; Whincup, Peter; Amouyel, Philippe; Giral, Philippe; Anugu, Pramod; Wong, Quenna; Malik, Rainer; Rauramaa, Rainer; Burkhardt, Ralph; Hardy, Rebecca; Schmidt, Reinhold; Mutsert, Renée; Morris, Richard; Strawbridge, Rona; Wannamethee, S.; Hägg, Sara; Shah, Sonia; McLachlan, Stela; Trompet, Stella; Seshadri, Sudha; Kurl, Sudhir; Heckbert, Susan; Ring, Susan; Harris, Tamara; Lehtimäki, Terho; Galesloot, Tessel; Shah, Tina; Faire, Ulf; Plagnol, Vincent; Rosamond, Wayne; Post, Wendy; Zhu, Xiaofeng; Zhang, Xiaoling; Guo, Xiuqing; Saba, Yasaman; Dehghan, Abbas; Seldenrijk, Adrie; Morrison, Alanna; Hamsten, Anders; Psaty, Bruce; Duijn, Cornelia; Lawlor, Deborah; Mook-Kanamori, Dennis; Bowden, Donald; Schmidt, Helena; Wilson, James; Wilson, James; Rotter, Jerome; Wardlaw, Joanna; Deanfield, John; Halcox, Julian; Lyytikäinen, Leo-Pekka; Loeffler, Markus; Evans, Michele; Debette, Stéphanie; Humphries, Steve; Völker, Uwe; Gudnason, Vilmundur; Hingorani, Aroon; Björkegren, Johan; Casas, Juan; O'Donnell, Christopher;
• Is Part Of: Nature communications. Volume 9:Issue 1(2018)
• Page Start: 1
• Page End: 14
• Publication Date: 2018-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-018-07340-5
• Languages: English
• ISSNs: 2041-1723

Abstract

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-identifiedPINX1 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 andLOXL4 . 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. Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.