Meta-Analysis

. 2018 Dec 3;9(1):5141.

doi: 10.1038/s41467-018-07340-5.

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

Nora Franceschini¹, Claudia Giambartolomei², Paul S de Vries³, Chris Finan⁴, Joshua C Bis⁵, Rachael P Huntley⁴, Ruth C Lovering⁴, Salman M Tajuddin⁶, Thomas W Winkler⁷, Misa Graff¹, Maryam Kavousi⁸, Caroline Dale⁹, Albert V Smith^{10

11}, Edith Hofer^{12

13}, Elisabeth M van Leeuwen⁸, Ilja M Nolte¹⁴, Lingyi Lu¹⁵, Markus Scholz^{16

17}, Muralidharan Sargurupremraj¹⁸, Niina Pitkänen¹⁹, Oscar Franzén^{20

21}, Peter K Joshi²², Raymond Noordam²³, Riccardo E Marioni^{24

25}, Shih-Jen Hwang^{26

27}, Solomon K Musani²⁸, Ulf Schminke²⁹, Walter Palmas³⁰, Aaron Isaacs^{8

31}, Adolfo Correa²⁸, Alan B Zonderman⁶, Albert Hofman^{8

32}, Alexander Teumer^{33

34}, Amanda J Cox^{35

36}, André G Uitterlinden^{8

37}, Andrew Wong³⁸, Andries J Smit³⁹, Anne B Newman⁴⁰, Annie Britton⁴¹, Arno Ruusalepp^{21

42

43}, Bengt Sennblad^{44

45}, Bo Hedblad⁴⁶, Bogdan Pasaniuc^{2

47}, Brenda W Penninx⁴⁸, Carl D Langefeld¹⁵, Christina L Wassel⁴⁹, Christophe Tzourio¹⁸, Cristiano Fava^{46

50}, Damiano Baldassarre^{51

52}, Daniel H O'Leary⁵³, Daniel Teupser^{17

54}, Diana Kuh³⁸, Elena Tremoli^{52

55}, Elmo Mannarino⁵⁶, Enzo Grossi⁵⁷, Eric Boerwinkle^{3

58}, Eric E Schadt^{20

21}, Erik Ingelsson^{59

60

61}, Fabrizio Veglia⁵², Fernando Rivadeneira^{8

37}, Frank Beutner⁶², Ganesh Chauhan^{18

63}, Gerardo Heiss¹, Harold Snieder¹⁴, Harry Campbell²², Henry Völzke^{33

34}, Hugh S Markus⁶⁴, Ian J Deary^{24

65}, J Wouter Jukema⁶⁶, Jacqueline de Graaf⁶⁷, Jacqueline Price²², Janne Pott^{16

17}, Jemma C Hopewell⁶⁸, Jingjing Liang⁶⁹, Joachim Thiery^{17

70}, Jorgen Engmann⁴, Karl Gertow⁴⁴, Kenneth Rice⁷¹, Kent D Taylor⁷², Klodian Dhana⁷³, Lambertus A L M Kiemeney⁷⁴, Lars Lind⁷⁵, Laura M Raffield⁷⁶, Lenore J Launer⁶, Lesca M Holdt^{17

54}, Marcus Dörr^{34

77}, Martin Dichgans^{78

79}, Matthew Traylor⁶⁴, Matthias Sitzer⁸⁰, Meena Kumari^{41

81}, Mika Kivimaki⁴¹, Mike A Nalls^{82

83}, Olle Melander⁴⁶, Olli Raitakari^{19

84}, Oscar H Franco^{8

85}, Oscar L Rueda-Ochoa^{8

86}, Panos Roussos^{20

87

88}, Peter H Whincup⁸⁹, Philippe Amouyel^{90

91

92}, Philippe Giral⁹³, Pramod Anugu²⁸, Quenna Wong⁹⁴, Rainer Malik⁷⁸, Rainer Rauramaa^{95

96}, Ralph Burkhardt^{17

97

98}, Rebecca Hardy³⁸, Reinhold Schmidt¹², Renée de Mutsert⁹⁹, Richard W Morris¹⁰⁰, Rona J Strawbridge^{44

101}, S Goya Wannamethee¹⁰², Sara Hägg¹⁰³, Sonia Shah⁴, Stela McLachlan²², Stella Trompet^{23

66}, Sudha Seshadri¹⁰⁴, Sudhir Kurl¹⁰⁵, Susan R Heckbert^{5

106}, Susan Ring^{107

108}, Tamara B Harris⁶, Terho Lehtimäki^{109

110}, Tessel E Galesloot⁷⁴, Tina Shah⁴, Ulf de Faire^{111

112}, Vincent Plagnol¹¹³, Wayne D Rosamond¹, Wendy Post¹¹⁴, Xiaofeng Zhu⁶⁹, Xiaoling Zhang^{27

115}, Xiuqing Guo^{72

116}, Yasaman Saba¹¹⁷; MEGASTROKE Consortium; Abbas Dehghan^{8

118}, Adrie Seldenrijk¹¹⁹, Alanna C Morrison³, Anders Hamsten⁴⁴, Bruce M Psaty^{106

120}, Cornelia M van Duijn^{8

68}, Deborah A Lawlor^{107

108}, Dennis O Mook-Kanamori^{99

121}, Donald W Bowden¹²², Helena Schmidt¹¹⁷, James F Wilson^{22

123}, James G Wilson¹²⁴, Jerome I Rotter^{72

116}, Joanna M Wardlaw^{24

125}, John Deanfield⁴, Julian Halcox¹²⁶, Leo-Pekka Lyytikäinen^{109

110}, Markus Loeffler^{16

17}, Michele K Evans⁶, Stéphanie Debette¹⁸, Steve E Humphries¹²⁷, Uwe Völker^{34

128}, Vilmundur Gudnason^{10

11}, Aroon D Hingorani⁴, Johan L M Björkegren^{129

130

131

132}, Juan P Casas⁹, Christopher J O'Donnell^{133

134

135}

Collaborators, Affiliations

Collaborators

MEGASTROKE Consortium:
Yukinori Okada, Aniket Mishra, Loes Rutten-Jacobs, Anne-Katrin Giese, Sander W van der Laan, Solveig Gretarsdottir, Christopher D Anderson, Michael Chong, Hieab H H Adams, Tetsuro Ago, Peter Almgren, Philippe Amouyel, Hakan Ay, Traci M Bartz, Oscar R Benavente, Steve Bevan, Giorgio B Boncoraglio, Robert D Brown Jr, Adam S Butterworth, Caty Carrera, Cara L Carty, Daniel I Chasman, Wei-Min Chen, John W Cole, Ioana Cotlarciuc, Carlos Cruchaga, John Danesh, Paul I W de Bakker, Anita L DeStefano, Marcel den Hoed, Qing Duan, Stefan T Engelter, Guido J Falcone, Rebecca F Gottesman, Raji P Grewal, Stefan Gustafsson, Jeffrey Haessler, Tamara B Harris, Ahamad Hassan, Aki S Havulinna, Elizabeth G Holliday, George Howard, Fang-Chi Hsu, Hyacinth I Hyacinth, M Arfan Ikram, Marguerite R Irvin, Xueqiu Jian, Jordi Jiménez-Conde, Julie A Johnson, J Wouter Jukema, Masahiro Kanai, Keith L Keene, Brett M Kissela, Dawn O Kleindorfer, Charles Kooperberg, Michiaki Kubo, Leslie Lange, Carl D Langefeld, Claudia Langenberg, Jin-Moo Lee, Robin Lemmens, Didier Leys, Cathryn M Lewis, Wei-Yu Lin, Arne G Lindgren, Erik Lorentzen, Patrik K Magnusson, Jane Maguire, Ani Manichaikul, Patrick F McArdle, James F Meschia, Thomas H Mosley, Toshiharu Ninomiya, Martin J O'Donnell, Sara L Pulit, Kristiina Rannikmäe, Alexander P Reiner, Kathryn M Rexrode, Stephen S Rich, Paul M Ridker, Natalia S Rost, Peter M Rothwell, Tatjana Rundek, Ralph L Sacco, Saori Sakaue, Michele M Sale, Veikko Salomaa, Bishwa R Sapkota, Reinhold Schmidt, Carsten O Schmidt, Ulf Schminke, Pankaj Sharma, Agnieszka Slowik, Cathie L M Sudlow, Christian Tanislav, Turgut Tatlisumak, Vincent N S Thijs, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Steffen Tiedt, Stella Trompet, Matthew Walters, Nicholas J Wareham, Sylvia Wassertheil-Smoller, Kerri L Wiggins, Qiong Yang, Salim Yusuf, Tomi Pastinen, Arno Ruusalepp, Eric E Schadt, Simon Koplev, Veronica Codoni, Mete Civelek, Nick Smith, David A Trégouët, Ingrid E Christophersen, Carolina Roselli, Steven A Lubitz, Patrick T Ellinor, E Shyong Tai, Jaspal S Kooner, Norihiro Kato, Jiang He, Pim van der Harst, Paul Elliott, John C Chambers, Fumihiko Takeuchi, Andrew D Johnson, Dharambir K Sanghera, Olle Melander, Christina Jern, Daniel Strbian, Israel Fernandez-Cadenas, W T Longstreth Jr, Arndt Rolfs, Jun Hata, Daniel Woo, Jonathan Rosand, Guillaume Pare, Danish Saleheen, Kari Stefansson, Bradford B Worrall, Steven J Kittner, Joanna M M Howson, Yoichiro Kamatani

Affiliations

¹ Department of Epidemiology, University of North Carolina, Chapel Hill, NC, 27516, USA.
² Department of Pathology and Laboratory Medicine, University of California (UCLA), Los Angeles, Los Angeles, CA, 90095, USA.
³ Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
⁴ Institute of Cardiovascular Science, University College London, London, WC1 6BT, UK.
⁵ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98101, USA.
⁶ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 20892, USA.
⁷ Department of Genetic Epidemiology, University of Regensburg, Regensburg, 93053, Germany.
⁸ Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015, The Netherlands.
⁹ Institute of Health Informatics, University College London, London, WC1E 6BT, UK.
¹⁰ Icelandic Heart Association, Kopavogur, IS-201, Iceland.
¹¹ University of Iceland, Reykjavik, 101, Iceland.
¹² Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, 8036, Austria.
¹³ Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, 8036, Austria.
¹⁴ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 3015, The Netherlands.
¹⁵ Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
¹⁶ Institute for Medical Informatics, Statistics and Epidemiology, , University of Leipzig, Leipzig, 04107, Germany.
¹⁷ LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, 04107, Germany.
¹⁸ Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux, F-33000, Bordeaux, France.
¹⁹ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, 20520, Finland.
²⁰ Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
²¹ Clinical Gene Networks AB, Stockholm, 104 62, Sweden.
²² Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
²³ Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, 2300, RC, The Netherlands.
²⁴ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
²⁵ Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
²⁶ Population Sciences Branch, Division of Intramural Research, NHLBI, NIH, Framingham, MA, 01702-5827, USA.
²⁷ National Heart, Lung and Blood Institute's Intramural Research Program, Framingham Heart Study, Framingham, MA, 01702-5827, USA.
²⁸ Department of Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
²⁹ Department of Neurology, University Medicine Greifswald, Greifswald, 17475, Germany.
³⁰ Department of Medicine, Columbia University, New York, NY, 10032, USA.
³¹ Department of Biochemistry, Maastricht Centre for Systems Biology (MaCSBio), CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, 6229, The Netherlands.
³² Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
³³ Institute for Community Medicine, University Medicine Greifswald, Greifswald, 17475, Germany.
³⁴ DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, 17475, Germany.
³⁵ Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, 25157, USA.
³⁶ Menzies Health Institute Queensland, Griffith University, Southport, QLD, 4222, Australia.
³⁷ Department of Internal Medicine, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, 3015, The Netherlands.
³⁸ MRC Unit for Lifelong Health and Ageing at UCL, London, WC1E 6BT, UK.
³⁹ Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, 2300, The Netherlands.
⁴⁰ Department of Epidemiology, and School of Medicine, Division of Geriatric Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
⁴¹ Department of Epidemiology and Public Health, University College London, London, WC1E 6BT, UK.
⁴² Department of Pathophysiology, Institute of Biomedicine and Translation Medicine, University of Tartu, Biomeedikum, Tartu, 51010, Estonia.
⁴³ Department of Cardiac Surgery, Tartu University Hospital, Tartu, 51010, Estonia.
⁴⁴ Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, 17177, Sweden.
⁴⁵ Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, 75108, Sweden.
⁴⁶ Department of Clinical Sciences in Malmö, Lund University, Malmö, SE-205 02, Sweden.
⁴⁷ Department of Human Genetics, University of California (UCLA), Los Angeles, CA, 90095, USA.
⁴⁸ Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, 1081, HL, The Netherlands.
⁴⁹ Applied Sciences, Premier, Inc., Charlotte, NC, 28277, USA.
⁵⁰ Department of Medicine, University of Verona, Verona, 37134, Italy.
⁵¹ Department of Medical Biotechnology and Translational Medicine, Università di Milano, Milan, 20133, Italy.
⁵² Centro Cardiologico Monzino, IRCCS, Milan, 20138, Italy.
⁵³ St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, 02135, USA.
⁵⁴ Institute of Laboratory Medicine, University Hospital Munich, LMU Munich, 80539, Germany.
⁵⁵ Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, 20133, Italy.
⁵⁶ Department of Clinical and Experimental Medicine, Internal Medicine, Angiology and Arteriosclerosis Diseases, University of Perugia, Perugia, 06123, Italy.
⁵⁷ Centro Diagnostico Italiano, Milan, 20147, Italy.
⁵⁸ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030-3411, USA.
⁵⁹ Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94309, USA.
⁶⁰ Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, 75185, Sweden.
⁶¹ Stanford Cardiovascular Institute, Stanford University, Stanford, CA, G1120, USA.
⁶² Heart Center Leipzig, Leipzig, 04103, Germany.
⁶³ Centre for Brain Research, Indian Institute of Science, Bangalore, 560012, India.
⁶⁴ Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, UK.
⁶⁵ Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
⁶⁶ Department of Cardiology, Leiden University Medical Center, Leiden, 2300, RC, The Netherlands.
⁶⁷ Department of Internal Medicine, Radboud University Medical Center, Nijmegen, 6525, GA, The Netherlands.
⁶⁸ Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
⁶⁹ Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.
⁷⁰ Institute for Laboratory Medicine, University of Leipzig, Leipzig, 04109, Germany.
⁷¹ Department of Biostatistics, University of Washington, Seattle, WA, 98105, USA.
⁷² Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
⁷³ Department of Internal Medicine, Rush University Medical Center, Chicago, IL, 60612, USA.
⁷⁴ Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, GA, 6525, The Netherlands.
⁷⁵ Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, 751 05, Sweden.
⁷⁶ Department of Genetics, University of North Carolina, Chapel Hill, NC, 27516, USA.
⁷⁷ Department of Internal Medicine B, University Medicine Greifswald, Greifswald, 17475, Germany.
⁷⁸ Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University (LMU), Munich, 80539, Germany.
⁷⁹ Munich Cluster for Systems Neurology (SyNergy), Munich, 81377, Germany.
⁸⁰ Department of Neurology, Center for Neurology and Neurosurgery, Johann Wolfgang Goethe-University, Frankfurt am Main, 60323, Germany.
⁸¹ Institute for Social and Economic Research, Essex University, Colchester, CO4 3SQ, UK.
⁸² Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA.
⁸³ Data Tecnica International, Glen Echo, MD, 20812, USA.
⁸⁴ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, 20521, Finland.
⁸⁵ Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, 3012, Switzerland.
⁸⁶ Electrocardiography Research Group, School of Medicine, Universidad Industrial de Santander, Bucaramanga, Santander, 680003, Colombia.
⁸⁷ Department of Psychiatry and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
⁸⁸ Mental Illness Research Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, New York, NY, 10468, USA.
⁸⁹ Population Health Research Institute, St George's, University of London, London, SW17 0RE, UK.
⁹⁰ Inserm U1167, F-59000, Lille, France.
⁹¹ Institut Pasteur de Lille, U1167, F-59000, Lille, France.
⁹² Université de Lille, U1167 - RID-AGE & Centre Hospitalier Universitaire de Lille, U1167, F-59000, Lille, France.
⁹³ Sorbonne Université, Cardiovascular Prevention Unit, Pitié Salpétrière Hospital, Paris, 75013, France.
⁹⁴ Collaborative Health Studies Coordinating Center, Department of Biostatistics, University of Washington, Seattle, WA, 98195, USA.
⁹⁵ Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland.
⁹⁶ Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, 70210, Finland.
⁹⁷ Institute of Laboratory Medicine, University of Leipzig, Leipzig, 04109, Germany.
⁹⁸ Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, 93053, Germany.
⁹⁹ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333, The Netherlands.
¹⁰⁰ Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 1QU, UK.
¹⁰¹ Mental Health and Wellbeing, Institute of Health and Wellbeing, University of Glasgow, Glasgow, G12 0XH, UK.
¹⁰² Department of Primary Care & Population Health, University College London, London, WC1E 6BT, UK.
¹⁰³ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SE-171 77, Sweden.
¹⁰⁴ Department of Neurology, Boston University School of Medicine, Boston, MA, 02118, USA.
¹⁰⁵ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, Kuopio, FI-70210, Finland.
¹⁰⁶ Kaiser Permanente Washington Health Research Institute, Seattle, WA, 98101, USA.
¹⁰⁷ Population Health Science, Bristol Medical School, University of Bristol, Bristol, BS8 1QU, UK.
¹⁰⁸ MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, BS8 1TH, UK.
¹⁰⁹ Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33014, Finland.
¹¹⁰ Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, 33014, Finland.
¹¹¹ Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, S-171 77, Sweden.
¹¹² Department of Cardiology, Karolinska University Hospital, Stockholm, S-171 77, Sweden.
¹¹³ Genetics Institute, University College London, London, WC1E 6BT, UK.
¹¹⁴ Departments of Medicine and Epidemiology, Johns Hopkins University, Baltimore, MD, 21205, USA.
¹¹⁵ Section of Biomedical Genetics, School of Medicine, Boston University, Boston, MA, 02215, USA.
¹¹⁶ Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
¹¹⁷ Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, 8010, Austria.
¹¹⁸ Department of Epidemiology & Biostatistics, Imperial College London, London, SW7 2AZ, UK.
¹¹⁹ GGZ inGeest and Amsterdam Public Health Research Institute, Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, 1081 HV, The Netherlands.
¹²⁰ Cardiovascular Health Research Unit and Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, 98195, USA.
¹²¹ Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
¹²² Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
¹²³ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK.
¹²⁴ Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
¹²⁵ Centre for Clinical Brain Sciences, and UK Dementia Research Institute at the University of Edinburgh, Edinburgh, EH16 4SB, UK.
¹²⁶ Swansea University Medical School, Swansea, SA2 8PP, UK.
¹²⁷ Centre for Cardiovascular Genetics, Institute Cardiovascular Science, University College London, London, WC1E 6BT, UK.
¹²⁸ Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, 17475, Germany.
¹²⁹ Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. johan.bjorkegren@mssm.edu.
¹³⁰ Clinical Gene Networks AB, Stockholm, 104 62, Sweden. johan.bjorkegren@mssm.edu.
¹³¹ Department of Pathophysiology, Institute of Biomedicine and Translation Medicine, University of Tartu, Biomeedikum, Tartu, 51010, Estonia. johan.bjorkegren@mssm.edu.
¹³² Integrated Cardio Metabolic Centre, Department of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, SE-141 57, Sweden. johan.bjorkegren@mssm.edu.
¹³³ Intramural Administration Management Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, 20892, USA. Christopher.ODonnell@va.gov.
¹³⁴ Cardiology Section, Boston Veteran's Administration Healthcare, Boston, MA, 02130, USA. Christopher.ODonnell@va.gov.
¹³⁵ Harvard Medical School, Boston, MA, 02115, USA. Christopher.ODonnell@va.gov.

PMID: 30510157
PMCID: PMC6277418
DOI: 10.1038/s41467-018-07340-5

Meta-Analysis

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

Nora Franceschini et al. Nat Commun. 2018.

. 2018 Dec 3;9(1):5141.

doi: 10.1038/s41467-018-07340-5.

Authors

Collaborators

MEGASTROKE Consortium:
Yukinori Okada, Aniket Mishra, Loes Rutten-Jacobs, Anne-Katrin Giese, Sander W van der Laan, Solveig Gretarsdottir, Christopher D Anderson, Michael Chong, Hieab H H Adams, Tetsuro Ago, Peter Almgren, Philippe Amouyel, Hakan Ay, Traci M Bartz, Oscar R Benavente, Steve Bevan, Giorgio B Boncoraglio, Robert D Brown Jr, Adam S Butterworth, Caty Carrera, Cara L Carty, Daniel I Chasman, Wei-Min Chen, John W Cole, Ioana Cotlarciuc, Carlos Cruchaga, John Danesh, Paul I W de Bakker, Anita L DeStefano, Marcel den Hoed, Qing Duan, Stefan T Engelter, Guido J Falcone, Rebecca F Gottesman, Raji P Grewal, Stefan Gustafsson, Jeffrey Haessler, Tamara B Harris, Ahamad Hassan, Aki S Havulinna, Elizabeth G Holliday, George Howard, Fang-Chi Hsu, Hyacinth I Hyacinth, M Arfan Ikram, Marguerite R Irvin, Xueqiu Jian, Jordi Jiménez-Conde, Julie A Johnson, J Wouter Jukema, Masahiro Kanai, Keith L Keene, Brett M Kissela, Dawn O Kleindorfer, Charles Kooperberg, Michiaki Kubo, Leslie Lange, Carl D Langefeld, Claudia Langenberg, Jin-Moo Lee, Robin Lemmens, Didier Leys, Cathryn M Lewis, Wei-Yu Lin, Arne G Lindgren, Erik Lorentzen, Patrik K Magnusson, Jane Maguire, Ani Manichaikul, Patrick F McArdle, James F Meschia, Thomas H Mosley, Toshiharu Ninomiya, Martin J O'Donnell, Sara L Pulit, Kristiina Rannikmäe, Alexander P Reiner, Kathryn M Rexrode, Stephen S Rich, Paul M Ridker, Natalia S Rost, Peter M Rothwell, Tatjana Rundek, Ralph L Sacco, Saori Sakaue, Michele M Sale, Veikko Salomaa, Bishwa R Sapkota, Reinhold Schmidt, Carsten O Schmidt, Ulf Schminke, Pankaj Sharma, Agnieszka Slowik, Cathie L M Sudlow, Christian Tanislav, Turgut Tatlisumak, Vincent N S Thijs, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Steffen Tiedt, Stella Trompet, Matthew Walters, Nicholas J Wareham, Sylvia Wassertheil-Smoller, Kerri L Wiggins, Qiong Yang, Salim Yusuf, Tomi Pastinen, Arno Ruusalepp, Eric E Schadt, Simon Koplev, Veronica Codoni, Mete Civelek, Nick Smith, David A Trégouët, Ingrid E Christophersen, Carolina Roselli, Steven A Lubitz, Patrick T Ellinor, E Shyong Tai, Jaspal S Kooner, Norihiro Kato, Jiang He, Pim van der Harst, Paul Elliott, John C Chambers, Fumihiko Takeuchi, Andrew D Johnson, Dharambir K Sanghera, Olle Melander, Christina Jern, Daniel Strbian, Israel Fernandez-Cadenas, W T Longstreth Jr, Arndt Rolfs, Jun Hata, Daniel Woo, Jonathan Rosand, Guillaume Pare, Danish Saleheen, Kari Stefansson, Bradford B Worrall, Steven J Kittner, Joanna M M Howson, Yoichiro Kamatani

Affiliations

¹ Department of Epidemiology, University of North Carolina, Chapel Hill, NC, 27516, USA.
² Department of Pathology and Laboratory Medicine, University of California (UCLA), Los Angeles, Los Angeles, CA, 90095, USA.
³ Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
⁴ Institute of Cardiovascular Science, University College London, London, WC1 6BT, UK.
⁵ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, 98101, USA.
⁶ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 20892, USA.
⁷ Department of Genetic Epidemiology, University of Regensburg, Regensburg, 93053, Germany.
⁸ Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015, The Netherlands.
⁹ Institute of Health Informatics, University College London, London, WC1E 6BT, UK.
¹⁰ Icelandic Heart Association, Kopavogur, IS-201, Iceland.
¹¹ University of Iceland, Reykjavik, 101, Iceland.
¹² Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, 8036, Austria.
¹³ Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, 8036, Austria.
¹⁴ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, 3015, The Netherlands.
¹⁵ Department of Biostatistical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
¹⁶ Institute for Medical Informatics, Statistics and Epidemiology, , University of Leipzig, Leipzig, 04107, Germany.
¹⁷ LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, 04107, Germany.
¹⁸ Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, CHU Bordeaux, F-33000, Bordeaux, France.
¹⁹ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, 20520, Finland.
²⁰ Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
²¹ Clinical Gene Networks AB, Stockholm, 104 62, Sweden.
²² Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
²³ Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, 2300, RC, The Netherlands.
²⁴ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
²⁵ Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
²⁶ Population Sciences Branch, Division of Intramural Research, NHLBI, NIH, Framingham, MA, 01702-5827, USA.
²⁷ National Heart, Lung and Blood Institute's Intramural Research Program, Framingham Heart Study, Framingham, MA, 01702-5827, USA.
²⁸ Department of Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
²⁹ Department of Neurology, University Medicine Greifswald, Greifswald, 17475, Germany.
³⁰ Department of Medicine, Columbia University, New York, NY, 10032, USA.
³¹ Department of Biochemistry, Maastricht Centre for Systems Biology (MaCSBio), CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, 6229, The Netherlands.
³² Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA.
³³ Institute for Community Medicine, University Medicine Greifswald, Greifswald, 17475, Germany.
³⁴ DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, 17475, Germany.
³⁵ Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, 25157, USA.
³⁶ Menzies Health Institute Queensland, Griffith University, Southport, QLD, 4222, Australia.
³⁷ Department of Internal Medicine, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, 3015, The Netherlands.
³⁸ MRC Unit for Lifelong Health and Ageing at UCL, London, WC1E 6BT, UK.
³⁹ Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, 2300, The Netherlands.
⁴⁰ Department of Epidemiology, and School of Medicine, Division of Geriatric Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
⁴¹ Department of Epidemiology and Public Health, University College London, London, WC1E 6BT, UK.
⁴² Department of Pathophysiology, Institute of Biomedicine and Translation Medicine, University of Tartu, Biomeedikum, Tartu, 51010, Estonia.
⁴³ Department of Cardiac Surgery, Tartu University Hospital, Tartu, 51010, Estonia.
⁴⁴ Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, 17177, Sweden.
⁴⁵ Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, 75108, Sweden.
⁴⁶ Department of Clinical Sciences in Malmö, Lund University, Malmö, SE-205 02, Sweden.
⁴⁷ Department of Human Genetics, University of California (UCLA), Los Angeles, CA, 90095, USA.
⁴⁸ Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, 1081, HL, The Netherlands.
⁴⁹ Applied Sciences, Premier, Inc., Charlotte, NC, 28277, USA.
⁵⁰ Department of Medicine, University of Verona, Verona, 37134, Italy.
⁵¹ Department of Medical Biotechnology and Translational Medicine, Università di Milano, Milan, 20133, Italy.
⁵² Centro Cardiologico Monzino, IRCCS, Milan, 20138, Italy.
⁵³ St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, 02135, USA.
⁵⁴ Institute of Laboratory Medicine, University Hospital Munich, LMU Munich, 80539, Germany.
⁵⁵ Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, 20133, Italy.
⁵⁶ Department of Clinical and Experimental Medicine, Internal Medicine, Angiology and Arteriosclerosis Diseases, University of Perugia, Perugia, 06123, Italy.
⁵⁷ Centro Diagnostico Italiano, Milan, 20147, Italy.
⁵⁸ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030-3411, USA.
⁵⁹ Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, 94309, USA.
⁶⁰ Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, 75185, Sweden.
⁶¹ Stanford Cardiovascular Institute, Stanford University, Stanford, CA, G1120, USA.
⁶² Heart Center Leipzig, Leipzig, 04103, Germany.
⁶³ Centre for Brain Research, Indian Institute of Science, Bangalore, 560012, India.
⁶⁴ Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, UK.
⁶⁵ Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
⁶⁶ Department of Cardiology, Leiden University Medical Center, Leiden, 2300, RC, The Netherlands.
⁶⁷ Department of Internal Medicine, Radboud University Medical Center, Nijmegen, 6525, GA, The Netherlands.
⁶⁸ Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.
⁶⁹ Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.
⁷⁰ Institute for Laboratory Medicine, University of Leipzig, Leipzig, 04109, Germany.
⁷¹ Department of Biostatistics, University of Washington, Seattle, WA, 98105, USA.
⁷² Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
⁷³ Department of Internal Medicine, Rush University Medical Center, Chicago, IL, 60612, USA.
⁷⁴ Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, GA, 6525, The Netherlands.
⁷⁵ Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, 751 05, Sweden.
⁷⁶ Department of Genetics, University of North Carolina, Chapel Hill, NC, 27516, USA.
⁷⁷ Department of Internal Medicine B, University Medicine Greifswald, Greifswald, 17475, Germany.
⁷⁸ Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University (LMU), Munich, 80539, Germany.
⁷⁹ Munich Cluster for Systems Neurology (SyNergy), Munich, 81377, Germany.
⁸⁰ Department of Neurology, Center for Neurology and Neurosurgery, Johann Wolfgang Goethe-University, Frankfurt am Main, 60323, Germany.
⁸¹ Institute for Social and Economic Research, Essex University, Colchester, CO4 3SQ, UK.
⁸² Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA.
⁸³ Data Tecnica International, Glen Echo, MD, 20812, USA.
⁸⁴ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, 20521, Finland.
⁸⁵ Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, 3012, Switzerland.
⁸⁶ Electrocardiography Research Group, School of Medicine, Universidad Industrial de Santander, Bucaramanga, Santander, 680003, Colombia.
⁸⁷ Department of Psychiatry and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
⁸⁸ Mental Illness Research Education and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx, New York, NY, 10468, USA.
⁸⁹ Population Health Research Institute, St George's, University of London, London, SW17 0RE, UK.
⁹⁰ Inserm U1167, F-59000, Lille, France.
⁹¹ Institut Pasteur de Lille, U1167, F-59000, Lille, France.
⁹² Université de Lille, U1167 - RID-AGE & Centre Hospitalier Universitaire de Lille, U1167, F-59000, Lille, France.
⁹³ Sorbonne Université, Cardiovascular Prevention Unit, Pitié Salpétrière Hospital, Paris, 75013, France.
⁹⁴ Collaborative Health Studies Coordinating Center, Department of Biostatistics, University of Washington, Seattle, WA, 98195, USA.
⁹⁵ Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland.
⁹⁶ Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, 70210, Finland.
⁹⁷ Institute of Laboratory Medicine, University of Leipzig, Leipzig, 04109, Germany.
⁹⁸ Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, 93053, Germany.
⁹⁹ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333, The Netherlands.
¹⁰⁰ Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 1QU, UK.
¹⁰¹ Mental Health and Wellbeing, Institute of Health and Wellbeing, University of Glasgow, Glasgow, G12 0XH, UK.
¹⁰² Department of Primary Care & Population Health, University College London, London, WC1E 6BT, UK.
¹⁰³ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SE-171 77, Sweden.
¹⁰⁴ Department of Neurology, Boston University School of Medicine, Boston, MA, 02118, USA.
¹⁰⁵ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio Campus, Kuopio, FI-70210, Finland.
¹⁰⁶ Kaiser Permanente Washington Health Research Institute, Seattle, WA, 98101, USA.
¹⁰⁷ Population Health Science, Bristol Medical School, University of Bristol, Bristol, BS8 1QU, UK.
¹⁰⁸ MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, BS8 1TH, UK.
¹⁰⁹ Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33014, Finland.
¹¹⁰ Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, 33014, Finland.
¹¹¹ Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, S-171 77, Sweden.
¹¹² Department of Cardiology, Karolinska University Hospital, Stockholm, S-171 77, Sweden.
¹¹³ Genetics Institute, University College London, London, WC1E 6BT, UK.
¹¹⁴ Departments of Medicine and Epidemiology, Johns Hopkins University, Baltimore, MD, 21205, USA.
¹¹⁵ Section of Biomedical Genetics, School of Medicine, Boston University, Boston, MA, 02215, USA.
¹¹⁶ Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
¹¹⁷ Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, 8010, Austria.
¹¹⁸ Department of Epidemiology & Biostatistics, Imperial College London, London, SW7 2AZ, UK.
¹¹⁹ GGZ inGeest and Amsterdam Public Health Research Institute, Department of Psychiatry, Amsterdam University Medical Center, Amsterdam, 1081 HV, The Netherlands.
¹²⁰ Cardiovascular Health Research Unit and Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, 98195, USA.
¹²¹ Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.
¹²² Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
¹²³ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK.
¹²⁴ Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
¹²⁵ Centre for Clinical Brain Sciences, and UK Dementia Research Institute at the University of Edinburgh, Edinburgh, EH16 4SB, UK.
¹²⁶ Swansea University Medical School, Swansea, SA2 8PP, UK.
¹²⁷ Centre for Cardiovascular Genetics, Institute Cardiovascular Science, University College London, London, WC1E 6BT, UK.
¹²⁸ Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, 17475, Germany.
¹²⁹ Department of Genetics and Genomic Sciences, The Icahn Institute for Genomics and Multiscale Biology Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. johan.bjorkegren@mssm.edu.
¹³⁰ Clinical Gene Networks AB, Stockholm, 104 62, Sweden. johan.bjorkegren@mssm.edu.
¹³¹ Department of Pathophysiology, Institute of Biomedicine and Translation Medicine, University of Tartu, Biomeedikum, Tartu, 51010, Estonia. johan.bjorkegren@mssm.edu.
¹³² Integrated Cardio Metabolic Centre, Department of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, SE-141 57, Sweden. johan.bjorkegren@mssm.edu.
¹³³ Intramural Administration Management Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, 20892, USA. Christopher.ODonnell@va.gov.
¹³⁴ Cardiology Section, Boston Veteran's Administration Healthcare, Boston, MA, 02130, USA. Christopher.ODonnell@va.gov.
¹³⁵ Harvard Medical School, Boston, MA, 02115, USA. Christopher.ODonnell@va.gov.

PMID: 30510157
PMCID: PMC6277418
DOI: 10.1038/s41467-018-07340-5

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.

PubMed Disclaimer

Conflict of interest statement

C.F. received a fee for speaking at a course by Springer Healthcare/Malesci. E.I. is a scientific advisor for Precision Wellness, Cellink and Olink Proteomics for work unrelated to the present project. M.A.N.’s participation in this project was supported by a consulting contract between Data Tecnica International and the National Institute on Aging, NIH, Bethesda, MD, USA. M.A.N. also consults for Illumina Inc., the Michael J. Fox Foundation, and University of California Healthcare. B.M.P. serves on the DSMB of a clinical trial funded by Zoll LifeCor and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. D.A.L. has received support from Roche Diagnostics and Medtronic for biomarker research unrelated to this paper. J.P.C. has received funding from GSK regarding methodological work around electronic health records, and -omics for drug discovery. All remaining authors declare no competing interests.

Figures

**Fig. 1**
Overall study design. a GWAS meta-analyses of cIMT and carotid plaque for gene discovery. b Local and genome-wide shared genetic basis using gene expression and clinical outcomes GWAS data

**Fig. 2**
Pairwise colocalization results for genes identified for cIMT and carotid plaque GWAS meta-analysis with STARNET expression datasets. Red indicates a high posterior probability of colocalization and blue a high probability of no colocalization of the same SNP with tissue eQTLs

**Fig. 3**
Association results at the *CCDC71L* locus (chromosome 7), showing a high posterior probability of a shared variant for cIMT and carotid plaque in AOR and MAM eQTLs. −log10(p) SNP association p-values for cIMT (plot A) and carotid plaque (plot B), and eQTL in AOR (plot C) and eQTL in SF (plot D). Association results in SF tissue have a low probability of a shared signal with cIMT and carotid plaque, possibly indicating a different mechanism in this tissue. eQTLs in MAM are identical to AOR and not shown. The p-values were calculated by fitting a linear regression model with cIMT or plaque as dependent variable and imputed SNPs as independent variables. Each dot is an SNP and the color indicates linkage disequilibrium (r²) with the best hit (in purple)

See this image and copyright information in PMC

References

1. Mozaffarian D, et al. Heart Disease and Stroke Statistics-2016 Update: a report from the American Heart Association. Circulation. 2016;133:e38–e360. - PubMed
1. Frieden TR, Berwick DM. The Million Hearts initiative--preventing heart attacks and strokes. N. Engl. J. Med. 2011;365:e27. doi: 10.1056/NEJMp1110421. - DOI - PubMed
1. O’Donnell CJ, Nabel EG. Genomics of cardiovascular disease. N. Engl. J. Med. 2011;365:2098–2109. doi: 10.1056/NEJMra1105239. - DOI - PubMed
1. Bis JC, et al. Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque. Nat. Genet. 2011;43:940–947. doi: 10.1038/ng.920. - DOI - PMC - PubMed
1. Natarajan, P. et al. Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis. Circ. Cardiovasc. Genet.9, 511–520 (2016). - PMC - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials