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Large-scale association analysis identifies new risk loci for coronary artery disease

Author:
  • Panos Deloukas
  • Stavroula Kanoni
  • Christina Willenborg
  • Martin Farrall
  • Themistocles L. Assimes
  • John R. Thompson
  • Erik Ingelsson
  • Danish Saleheen
  • Jeanette Erdmann
  • Benjamin A. Goldstein
  • Kathleen Stirrups
  • Inke R. Koenig
  • Jean-Baptiste Cazier
  • Asa Johansson
  • Alistair S. Hall
  • Jong-Young Lee
  • Cristen J. Willer
  • John C. Chambers
  • Tonu Esko
  • Lasse Folkersen
  • Anuj Goel
  • Elin Grundberg
  • Aki S. Havulinna
  • Weang K. Ho
  • Jemma C. Hopewell
  • Niclas Eriksson
  • Marcus E. Kleber
  • Kati Kristiansson
  • Per Lundmark
  • Leo-Pekka Lyytikainen
  • Suzanne Rafelt
  • Dmitry Shungin
  • Rona J. Strawbridge
  • Gudmar Thorleifsson
  • Emmi Tikkanen
  • Natalie Van Zuydam
  • Benjamin F. Voight
  • Lindsay L. Waite
  • Weihua Zhang
  • Andreas Ziegler
  • Devin Absher
  • David Altshuler
  • Anthony J. Balmforth
  • Ines Barroso
  • Peter S. Braund
  • Christof Burgdorf
  • Simone Claudi-Boehm
  • David Cox
  • Maria Dimitriou
  • Ron Do
  • Alex S. F. Doney
  • NourEddine El Mokhtari
  • Per Eriksson
  • Krista Fischer
  • Pierre Fontanillas
  • Anders Franco-Cereceda
  • Bruna Gigante
  • Leif Groop
  • Stefan Gustafsson
  • Joerg Hager
  • Goran Hallmans
  • Bok-Ghee Han
  • Sarah E. Hunt
  • Hyun M. Kang
  • Thomas Illig
  • Thorsten Kessler
  • Joshua W. Knowles
  • Genovefa Kolovou
  • Johanna Kuusisto
  • Claudia Langenberg
  • Cordelia Langford
  • Karin Leander
  • Marja-Liisa Lokki
  • Anders Lundmark
  • Mark I. McCarthy
  • Christa Meisinger
  • Olle Melander
  • Evelin Mihailov
  • Seraya Maouche
  • Andrew D. Morris
  • Martina Mueller-Nurasyid
  • Kjell Nikus
  • John F. Peden
  • N. William Rayner
  • Asif Rasheed
  • Silke Rosinger
  • Diana Rubin
  • Moritz P. Rumpf
  • Arne Schaefer
  • Mohan Sivananthan
  • Ci Song
  • Alexandre F. R. Stewart
  • Sian-Tsung Tan
  • Gudmundur Thorgeirsson
  • C. Ellen van der Schoot
  • Peter J. Wagner
  • George A. Wells
  • Philipp S. Wild
  • Tsun-Po Yang
  • Philippe Amouyel
  • Dominique Arveiler
  • Hanneke Basart
  • Michael Boehnke
  • Eric Boerwinkle
  • Paolo Brambilla
  • Francois Cambien
  • Adrienne L. Cupples
  • Ulf de Faire
  • Abbas Dehghan
  • Patrick Diemert
  • Stephen E. Epstein
  • Alun Evans
  • Marco M. Ferrario
  • Jean Ferrieres
  • Dominique Gauguier
  • Alan S. Go
  • Alison H. Goodall
  • Villi Gudnason
  • Stanley L. Hazen
  • Hilma Holm
  • Carlos Iribarren
  • Yangsoo Jang
  • Mika Kahonen
  • Frank Kee
  • Hyo-Soo Kim
  • Norman Klopp
  • Wolfgang Koenig
  • Wolfgang Kratzer
  • Kari Kuulasmaa
  • Markku Laakso
  • Reijo Laaksonen
  • Ji-Young Lee
  • Lars Lind
  • Willem H. Ouwehand
  • Sarah Parish
  • Jeong E. Park
  • Nancy L. Pedersen
  • Annette Peters
  • Thomas Quertermous
  • Daniel J. Rader
  • Veikko Salomaa
  • Eric Schadt
  • Svati H. Shah
  • Juha Sinisalo
  • Klaus Stark
  • Kari Stefansson
  • David-Alexandre Tregouet
  • Jarmo Virtamo
  • Lars Wallentin
  • Nicholas Wareham
  • Martina E. Zimmermann
  • Markku S. Nieminen
  • Christian Hengstenberg
  • Manjinder S. Sandhu
  • Tomi Pastinen
  • Ann-Christine Syvanen
  • G. Kees Hovingh
  • George Dedoussis
  • Paul Franks
  • Terho Lehtimaki
  • Andres Metspalu
  • Pierre A. Zalloua
  • Agneta Siegbahn
  • Stefan Schreiber
  • Samuli Ripatti
  • Stefan S. Blankenberg
  • Markus Perola
  • Robert Clarke
  • Bernhard O. Boehm
  • Christopher O'Donnell
  • Muredach P. Reilly
  • Winfried Maerz
  • Rory Collins
  • Sekar Kathiresan
  • Anders Hamsten
  • Jaspal S. Kooner
  • Unnur Thorsteinsdottir
  • John Danesh
  • Colin N. A. Palmer
  • Robert Roberts
  • Hugh Watkins
  • Heribert Schunkert
  • Nilesh J. Samani
Publishing year: 2013
Language: English
Pages: 25-33
Publication/Series: Nature Genetics
Volume: 45
Issue: 1
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

Keywords

  • Endocrinology and Diabetes
  • Cardiac and Cardiovascular Systems

Other

Published
  • Genetic and Molecular Epidemiology
  • Hypertension and Cardiovascular Disease
  • ISSN: 1546-1718
Paul Franks
E-mail: paul.franks [at] med.lu.se

Principal investigator

Genetic and Molecular Epidemiology

+46 40 39 11 49

60-12-021

33

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00