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

Authors :
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 A. L. M.
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 L. M.
Casas, Juan P.
O'Donnell, Christopher J.
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 A. L. M.
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 L. M.
Casas, Juan P.
O'Donnell, Christopher J.
Publication Year :
2018

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 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.

Details

Database :
OAIster
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1235206933
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1038.s41467-018-07340-5