Nature Communications (Dec 2018)
GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- Nora Franceschini,
- Claudia Giambartolomei,
- Paul S. de 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. van 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 de 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 de 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 de Faire,
- Vincent Plagnol,
- Wayne D. Rosamond,
- Wendy Post,
- Xiaofeng Zhu,
- Xiaoling Zhang,
- Xiuqing Guo,
- Yasaman Saba,
- MEGASTROKE Consortium,
- Abbas Dehghan,
- Adrie Seldenrijk,
- Alanna C. Morrison,
- Anders Hamsten,
- Bruce M. Psaty,
- Cornelia M. van 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,
- Christopher J. O’Donnell
Affiliations
- Nora Franceschini
- Department of Epidemiology, University of North Carolina
- Claudia Giambartolomei
- Department of Pathology and Laboratory Medicine, University of California (UCLA), Los Angeles
- Paul S. de Vries
- Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston
- Chris Finan
- Institute of Cardiovascular Science, University College London
- Joshua C. Bis
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Rachael P. Huntley
- Institute of Cardiovascular Science, University College London
- Ruth C. Lovering
- Institute of Cardiovascular Science, University College London
- Salman M. Tajuddin
- Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health
- Thomas W. Winkler
- Department of Genetic Epidemiology, University of Regensburg
- Misa Graff
- Department of Epidemiology, University of North Carolina
- Maryam Kavousi
- Department of Epidemiology, Erasmus Medical Center
- Caroline Dale
- Institute of Health Informatics, University College London
- Albert V. Smith
- Icelandic Heart Association
- Edith Hofer
- Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz
- Elisabeth M. van Leeuwen
- Department of Epidemiology, Erasmus Medical Center
- Ilja M. Nolte
- Department of Epidemiology, University of Groningen, University Medical Center Groningen
- Lingyi Lu
- Department of Biostatistical Sciences, Wake Forest University School of Medicine
- Markus Scholz
- Institute for Medical Informatics, Statistics and Epidemiology, , University of Leipzig
- Muralidharan Sargurupremraj
- Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux
- Niina Pitkänen
- Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku
- Oscar Franzén
- Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai
- Peter K. Joshi
- Usher Institute of Population Health Sciences and Informatics, University of Edinburgh
- Raymond Noordam
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center
- Riccardo E. Marioni
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh
- Shih-Jen Hwang
- Population Sciences Branch, Division of Intramural Research, NHLBI, NIH
- Solomon K. Musani
- Department of Medicine, University of Mississippi Medical Center
- Ulf Schminke
- Department of Neurology, University Medicine Greifswald
- Walter Palmas
- Department of Medicine, Columbia University
- Aaron Isaacs
- Department of Epidemiology, Erasmus Medical Center
- Adolfo Correa
- Department of Medicine, University of Mississippi Medical Center
- Alan B. Zonderman
- Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health
- Albert Hofman
- Department of Epidemiology, Erasmus Medical Center
- Alexander Teumer
- Institute for Community Medicine, University Medicine Greifswald
- Amanda J. Cox
- Center for Diabetes Research, Wake Forest School of Medicine
- André G. Uitterlinden
- Department of Epidemiology, Erasmus Medical Center
- Andrew Wong
- MRC Unit for Lifelong Health and Ageing at UCL
- Andries J. Smit
- Department of Medicine, University of Groningen, University Medical Center Groningen
- Anne B. Newman
- Department of Epidemiology, and School of Medicine, Division of Geriatric Medicine, University of Pittsburgh
- Annie Britton
- Department of Epidemiology and Public Health, University College London
- Arno Ruusalepp
- Clinical Gene Networks AB
- Bengt Sennblad
- Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet
- Bo Hedblad
- Department of Clinical Sciences in Malmö, Lund University
- Bogdan Pasaniuc
- Department of Pathology and Laboratory Medicine, University of California (UCLA), Los Angeles
- Brenda W. Penninx
- Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center
- Carl D. Langefeld
- Department of Biostatistical Sciences, 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
- Department of Clinical Sciences in Malmö, Lund University
- Damiano Baldassarre
- Department of Medical Biotechnology and Translational Medicine, Università di Milano
- Daniel H. O’Leary
- St. Elizabeth’s Medical Center, Tufts University School of Medicine
- Daniel Teupser
- LIFE Research Center for Civilization Diseases, University of Leipzig
- Diana Kuh
- MRC Unit for Lifelong Health and Ageing at UCL
- Elena Tremoli
- Centro Cardiologico Monzino, IRCCS
- Elmo Mannarino
- Department of Clinical and Experimental Medicine, Internal Medicine, Angiology and Arteriosclerosis Diseases, University of Perugia
- Enzo Grossi
- Centro Diagnostico Italiano
- Eric Boerwinkle
- Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston
- Eric E. Schadt
- Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai
- Erik Ingelsson
- Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine
- Fabrizio Veglia
- Centro Cardiologico Monzino, IRCCS
- Fernando Rivadeneira
- Department of Epidemiology, Erasmus Medical Center
- Frank Beutner
- Heart Center Leipzig
- Ganesh Chauhan
- Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux
- Gerardo Heiss
- Department of Epidemiology, University of North Carolina
- Harold Snieder
- Department of Epidemiology, University of Groningen, University Medical Center Groningen
- Harry Campbell
- Usher Institute of Population Health Sciences and Informatics, University of Edinburgh
- Henry Völzke
- Institute for Community Medicine, University Medicine Greifswald
- Hugh S. Markus
- Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge
- Ian J. Deary
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh
- J. Wouter Jukema
- Department of Cardiology, Leiden University Medical Center
- Jacqueline de Graaf
- Department of Internal Medicine, Radboud University Medical Center
- Jacqueline Price
- Usher Institute of Population Health Sciences and Informatics, University of Edinburgh
- Janne Pott
- Institute for Medical Informatics, Statistics and Epidemiology, , University of Leipzig
- Jemma C. Hopewell
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford
- Jingjing Liang
- Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University
- Joachim Thiery
- LIFE Research Center for Civilization Diseases, University of Leipzig
- Jorgen Engmann
- Institute of Cardiovascular Science, University College London
- Karl Gertow
- Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet
- Kenneth Rice
- Department of Biostatistics, 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
- Department of Internal Medicine, Rush University Medical Center
- Lambertus A. L. M. Kiemeney
- Radboud Institute for Health Sciences, Radboud University Medical Center
- Lars Lind
- Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University
- Laura M. Raffield
- Department of Genetics, University of North Carolina
- Lenore J. Launer
- Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health
- Lesca M. Holdt
- LIFE Research Center for Civilization Diseases, University of Leipzig
- Marcus Dörr
- DZHK (German Center for Cardiovascular Research), partner site Greifswald
- Martin Dichgans
- Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University (LMU)
- Matthew Traylor
- Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge
- Matthias Sitzer
- Department of Neurology, Center for Neurology and Neurosurgery, Johann Wolfgang Goethe-University
- Meena Kumari
- Department of Epidemiology and Public Health, University College London
- Mika Kivimaki
- Department of Epidemiology and Public Health, University College London
- Mike A. Nalls
- Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health
- Olle Melander
- Department of Clinical Sciences in Malmö, Lund University
- Olli Raitakari
- Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku
- Oscar H. Franco
- Department of Epidemiology, Erasmus Medical Center
- Oscar L. Rueda-Ochoa
- Department of Epidemiology, Erasmus Medical Center
- Panos Roussos
- Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai
- Peter H. Whincup
- Population Health Research Institute, St George’s, University of London
- Philippe Amouyel
- Inserm U1167
- Philippe Giral
- Sorbonne Université, Cardiovascular Prevention Unit, Pitié Salpétrière Hospital
- Pramod Anugu
- Department of Medicine, University of Mississippi Medical Center
- Quenna Wong
- Collaborative Health Studies Coordinating Center, Department of Biostatistics, University of Washington
- Rainer Malik
- Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University (LMU)
- Rainer Rauramaa
- Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine
- Ralph Burkhardt
- LIFE Research Center for Civilization Diseases, University of Leipzig
- Rebecca Hardy
- MRC Unit for Lifelong Health and Ageing at UCL
- Reinhold Schmidt
- Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz
- Renée de Mutsert
- Department of Clinical Epidemiology, Leiden University Medical Center
- Richard W. Morris
- Department of Population Health Sciences, Bristol Medical School, University of Bristol
- Rona J. Strawbridge
- Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet
- S. Goya Wannamethee
- Department of Primary Care & Population Health, University College London
- Sara Hägg
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet
- Sonia Shah
- Institute of Cardiovascular Science, University College London
- Stela McLachlan
- Usher Institute of Population Health Sciences and Informatics, University of Edinburgh
- Stella Trompet
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center
- Sudha Seshadri
- Department of Neurology, Boston University School of Medicine
- Sudhir Kurl
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus
- Susan R. Heckbert
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington
- Susan Ring
- Population Health Science, 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
- Department of Clinical Chemistry, Fimlab Laboratories
- Tessel E. Galesloot
- Radboud Institute for Health Sciences, Radboud University Medical Center
- Tina Shah
- Institute of Cardiovascular Science, University College London
- Ulf de Faire
- Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet
- Vincent Plagnol
- Genetics Institute, University College London
- Wayne D. Rosamond
- Department of Epidemiology, University of North Carolina
- Wendy Post
- Departments of Medicine and Epidemiology, Johns Hopkins University
- Xiaofeng Zhu
- Department of Population and Quantitative Health Sciences, School of Medicine, 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
- Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz
- MEGASTROKE Consortium
- Abbas Dehghan
- Department of Epidemiology, Erasmus Medical Center
- Adrie Seldenrijk
- GGZ inGeest and Amsterdam Public Health Research Institute, Department of Psychiatry, Amsterdam University Medical Center
- Alanna C. Morrison
- Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, 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. van Duijn
- Department of Epidemiology, Erasmus Medical Center
- Deborah A. Lawlor
- Population Health Science, Bristol Medical School, University of Bristol
- Dennis O. Mook-Kanamori
- Department of Clinical Epidemiology, Leiden University Medical Center
- Donald W. Bowden
- Center for Human Genomics, Wake Forest University School of Medicine
- Helena Schmidt
- Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz
- James F. Wilson
- Usher Institute of Population Health Sciences and Informatics, University of Edinburgh
- James G. Wilson
- Department of Physiology and Biophysics, 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
- Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh
- John Deanfield
- Institute of Cardiovascular Science, University College London
- Julian Halcox
- Swansea University Medical School
- Leo-Pekka Lyytikäinen
- Department of Clinical Chemistry, Fimlab Laboratories
- Markus Loeffler
- Institute for Medical Informatics, Statistics and Epidemiology, , 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
- Institute of Cardiovascular Science, University College London
- Johan L. M. Björkegren
- Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai
- Juan P. Casas
- Institute of Health Informatics, University College London
- Christopher J. O’Donnell
- Intramural Administration Management Branch, National Heart, Lung, and Blood Institute, NIH
- DOI
- https://doi.org/10.1038/s41467-018-07340-5
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 14
Abstract
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.
