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

Nora Franceschini, Claudia Giambartolomei, Paul S. Vries, Chris Finan, Joshua C. Bis, Rachael P. Huntley, Ruth C. Lovering, Salman M. Tajuddin, Thomas W. Winkler, Misa Graff, Maryam Kavousi, Caroline Dale, Albert V. Smith, Edith Hofer, Elisabeth M. Leeuwen, Ilja M. Nolte, Lingyi Lu, Markus Scholz, Muralidharan Sargurupremraj, Niina Pitkänen, Oscar Franzén, Peter K. Joshi, Raymond Noordam, Riccardo E. Marioni, Shih-Jen Hwang, Solomon K. Musani, Ulf Schminke, Walter Palmas, Aaron Isaacs, Adolfo Correa, Alan B. Zonderman, Albert Hofman, Alexander Teumer, Amanda J. Cox, André G. Uitterlinden, Andrew Wong, Andries J. Smit, Anne B. Newman, Annie Britton, Arno Ruusalepp, Bengt Sennblad, Bo Hedblad, Bogdan Pasaniuc, Brenda W. Penninx, Carl D. Langefeld, Christina L. Wassel, Christophe Tzourio, Cristiano Fava, Damiano Baldassarre, Daniel H. O’Leary, Daniel Teupser, Diana Kuh, Elena Tremoli, Elmo Mannarino, Enzo Grossi, Eric Boerwinkle, Eric E. Schadt, Erik Ingelsson, Fabrizio Veglia, Fernando Rivadeneira, Frank Beutner, Ganesh Chauhan, Gerardo Heiss, Harold Snieder, Harry Campbell, Henry Völzke, Hugh S. Markus, Ian J. Deary, J. Wouter Jukema, Jacqueline Graaf, Jacqueline Price, Janne Pott, Jemma C. Hopewell, Jingjing Liang, Joachim Thiery, Jorgen Engmann, Karl Gertow, Kenneth Rice, Kent D. Taylor, Klodian Dhana, Lambertus A. L. M. Kiemeney, Lars Lind, Laura M. Raffield, Lenore J. Launer, Lesca M. Holdt, Marcus Dörr, Martin Dichgans, Matthew Traylor, Matthias Sitzer, Meena Kumari, Mika Kivimaki, Mike A. Nalls, Olle Melander, Olli Raitakari, Oscar H. Franco, Oscar L. Rueda-Ochoa, Panos Roussos, Peter H. Whincup, Philippe Amouyel, Philippe Giral, Pramod Anugu, Quenna Wong, Rainer Malik, Rainer Rauramaa, Ralph Burkhardt, Rebecca Hardy, Reinhold Schmidt, Renée Mutsert, Richard W. Morris, Rona J. Strawbridge, S. Goya Wannamethee, Sara Hägg, Sonia Shah, Stela McLachlan, Stella Trompet, Sudha Seshadri, Sudhir Kurl, Susan R. Heckbert, Susan Ring, Tamara B. Harris, Terho Lehtimäki, Tessel E. Galesloot, Tina Shah, Ulf Faire, Vincent Plagnol, Wayne D. Rosamond, Wendy Post, Xiaofeng Zhu, Xiaoling Zhang, Xiuqing Guo, Yasaman Saba, Abbas Dehghan, Adrie Seldenrijk, Alanna C. Morrison, Anders Hamsten, Bruce M. Psaty, Cornelia M. Duijn, Deborah A. Lawlor, Dennis O. Mook-Kanamori, Donald W. Bowden, Helena Schmidt, James F. Wilson, James G. Wilson, Jerome I. Rotter, Joanna M. Wardlaw, John Deanfield, Julian Halcox, Leo-Pekka Lyytikäinen, Markus Loeffler, Michele K. Evans, Stéphanie Debette, Steve E. Humphries, Uwe Völker, Vilmundur Gudnason, Aroon D. Hingorani, Johan L. M. Björkegren (), Juan P. Casas and Christopher J. O’Donnell ()
Additional contact information
Nora Franceschini: University of North Carolina
Claudia Giambartolomei: University of California (UCLA), Los Angeles
Paul S. Vries: The University of Texas Health Science Center at Houston
Chris Finan: University College London
Joshua C. Bis: University of Washington
Rachael P. Huntley: University College London
Ruth C. Lovering: University College London
Salman M. Tajuddin: Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health
Thomas W. Winkler: University of Regensburg
Misa Graff: University of North Carolina
Maryam Kavousi: Erasmus Medical Center
Caroline Dale: University College London
Albert V. Smith: Icelandic Heart Association
Edith Hofer: Medical University of Graz
Elisabeth M. Leeuwen: Erasmus Medical Center
Ilja M. Nolte: University of Groningen, University Medical Center Groningen
Lingyi Lu: Wake Forest University School of Medicine
Markus Scholz: , University of Leipzig
Muralidharan Sargurupremraj: Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux
Niina Pitkänen: University of Turku
Oscar Franzén: The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai
Peter K. Joshi: University of Edinburgh
Raymond Noordam: Leiden University Medical Center
Riccardo E. Marioni: University of Edinburgh
Shih-Jen Hwang: Population Sciences Branch, Division of Intramural Research, NHLBI, NIH
Solomon K. Musani: University of Mississippi Medical Center
Ulf Schminke: University Medicine Greifswald
Walter Palmas: Columbia University
Aaron Isaacs: Erasmus Medical Center
Adolfo Correa: University of Mississippi Medical Center
Alan B. Zonderman: Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health
Albert Hofman: Erasmus Medical Center
Alexander Teumer: University Medicine Greifswald
Amanda J. Cox: Center for Diabetes Research, Wake Forest School of Medicine
André G. Uitterlinden: Erasmus Medical Center
Andrew Wong: MRC Unit for Lifelong Health and Ageing at UCL
Andries J. Smit: University of Groningen, University Medical Center Groningen
Anne B. Newman: University of Pittsburgh
Annie Britton: University College London
Arno Ruusalepp: Clinical Gene Networks AB
Bengt Sennblad: Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet
Bo Hedblad: Lund University
Bogdan Pasaniuc: University of California (UCLA), Los Angeles
Brenda W. Penninx: VU University Medical Center
Carl D. Langefeld: Wake Forest University School of Medicine
Christina L. Wassel: Applied Sciences, Premier, Inc.
Christophe Tzourio: Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux
Cristiano Fava: Lund University
Damiano Baldassarre: Università di Milano
Daniel H. O’Leary: Tufts University School of Medicine
Daniel Teupser: University of Leipzig
Diana Kuh: MRC Unit for Lifelong Health and Ageing at UCL
Elena Tremoli: Centro Cardiologico Monzino, IRCCS
Elmo Mannarino: University of Perugia
Enzo Grossi: Centro Diagnostico Italiano
Eric Boerwinkle: The University of Texas Health Science Center at Houston
Eric E. Schadt: The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai
Erik Ingelsson: Stanford University School of Medicine
Fabrizio Veglia: Centro Cardiologico Monzino, IRCCS
Fernando Rivadeneira: Erasmus Medical Center
Frank Beutner: Heart Center Leipzig
Ganesh Chauhan: Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux
Gerardo Heiss: University of North Carolina
Harold Snieder: University of Groningen, University Medical Center Groningen
Harry Campbell: University of Edinburgh
Henry Völzke: University Medicine Greifswald
Hugh S. Markus: University of Cambridge
Ian J. Deary: University of Edinburgh
J. Wouter Jukema: Leiden University Medical Center
Jacqueline Graaf: Radboud University Medical Center
Jacqueline Price: University of Edinburgh
Janne Pott: , University of Leipzig
Jemma C. Hopewell: University of Oxford
Jingjing Liang: Case Western Reserve University
Joachim Thiery: University of Leipzig
Jorgen Engmann: University College London
Karl Gertow: Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet
Kenneth Rice: University of Washington
Kent D. Taylor: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Klodian Dhana: Rush University Medical Center
Lambertus A. L. M. Kiemeney: Radboud University Medical Center
Lars Lind: Uppsala University
Laura M. Raffield: University of North Carolina
Lenore J. Launer: Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health
Lesca M. Holdt: University of Leipzig
Marcus Dörr: DZHK (German Center for Cardiovascular Research), partner site Greifswald
Martin Dichgans: University Hospital, Ludwig-Maximilians-University (LMU)
Matthew Traylor: University of Cambridge
Matthias Sitzer: Johann Wolfgang Goethe-University
Meena Kumari: University College London
Mika Kivimaki: University College London
Mike A. Nalls: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health
Olle Melander: Lund University
Olli Raitakari: University of Turku
Oscar H. Franco: Erasmus Medical Center
Oscar L. Rueda-Ochoa: Erasmus Medical Center
Panos Roussos: The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai
Peter H. Whincup: University of London
Philippe Amouyel: Inserm U1167
Philippe Giral: Sorbonne Université, Cardiovascular Prevention Unit, Pitié Salpétrière Hospital
Pramod Anugu: University of Mississippi Medical Center
Quenna Wong: University of Washington
Rainer Malik: University Hospital, Ludwig-Maximilians-University (LMU)
Rainer Rauramaa: Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine
Ralph Burkhardt: University of Leipzig
Rebecca Hardy: MRC Unit for Lifelong Health and Ageing at UCL
Reinhold Schmidt: Medical University of Graz
Renée Mutsert: Leiden University Medical Center
Richard W. Morris: Bristol Medical School, University of Bristol
Rona J. Strawbridge: Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet
S. Goya Wannamethee: University College London
Sara Hägg: Karolinska Institutet
Sonia Shah: University College London
Stela McLachlan: University of Edinburgh
Stella Trompet: Leiden University Medical Center
Sudha Seshadri: Boston University School of Medicine
Sudhir Kurl: University of Eastern Finland, Kuopio Campus
Susan R. Heckbert: University of Washington
Susan Ring: Bristol Medical School, University of Bristol
Tamara B. Harris: Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health
Terho Lehtimäki: Fimlab Laboratories
Tessel E. Galesloot: Radboud University Medical Center
Tina Shah: University College London
Ulf Faire: Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet
Vincent Plagnol: University College London
Wayne D. Rosamond: University of North Carolina
Wendy Post: Johns Hopkins University
Xiaofeng Zhu: Case Western Reserve University
Xiaoling Zhang: National Heart, Lung and Blood Institute’s Intramural Research Program, Framingham Heart Study
Xiuqing Guo: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Yasaman Saba: Medical University of Graz
Abbas Dehghan: Erasmus Medical Center
Adrie Seldenrijk: Amsterdam University Medical Center
Alanna C. Morrison: The University of Texas Health Science Center at Houston
Anders Hamsten: Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet
Bruce M. Psaty: Kaiser Permanente Washington Health Research Institute
Cornelia M. Duijn: Erasmus Medical Center
Deborah A. Lawlor: Bristol Medical School, University of Bristol
Dennis O. Mook-Kanamori: Leiden University Medical Center
Donald W. Bowden: Wake Forest University School of Medicine
Helena Schmidt: Medical University of Graz
James F. Wilson: University of Edinburgh
James G. Wilson: University of Mississippi Medical Center
Jerome I. Rotter: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Joanna M. Wardlaw: University of Edinburgh
John Deanfield: University College London
Julian Halcox: Swansea University Medical School
Leo-Pekka Lyytikäinen: Fimlab Laboratories
Markus Loeffler: , University of Leipzig
Michele K. Evans: Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health
Stéphanie Debette: Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux
Steve E. Humphries: Centre for Cardiovascular Genetics, Institute Cardiovascular Science, University College London
Uwe Völker: DZHK (German Center for Cardiovascular Research), partner site Greifswald
Vilmundur Gudnason: Icelandic Heart Association
Aroon D. Hingorani: University College London
Johan L. M. Björkegren: The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai
Juan P. Casas: University College London
Christopher J. O’Donnell: Intramural Administration Management Branch, National Heart, Lung, and Blood Institute, NIH

Nature Communications, 2018, vol. 9, issue 1, 1-14

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-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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-07340-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07340-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-07340-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().