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Olle Melander

Principal investigator

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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Author

  • Majid Nikpay
  • Anuj Goel
  • Hong-Hee Won
  • Leanne M. Hall
  • Christina Willenborg
  • Stavroula Kanoni
  • Danish Saleheen
  • Theodosios Kyriakou
  • Christopher P. Nelson
  • Jemma C. Hopewell
  • Thomas R. Webb
  • Lingyao Zeng
  • Abbas Dehghan
  • Maris Alver
  • Sebastian M. Armasu
  • Kirsi Auro
  • Andrew Bjonnes
  • Daniel I. Chasman
  • Shufeng Chen
  • Ian Ford
  • Nora Franceschini
  • Christian Gieger
  • Christopher Grace
  • Stefan Gustafsson
  • Jie Huang
  • Shih-Jen Hwang
  • Yun Kyoung Kim
  • Marcus E. Kleber
  • King Wai Lau
  • Xiangfeng Lu
  • Yingchang Lu
  • Leo-Pekka Lyytikainen
  • Evelin Mihailov
  • Alanna C. Morrison
  • Natalia Pervjakova
  • Liming Qu
  • Lynda M. Rose
  • Elias Salfati
  • Richa Saxena
  • Markus Scholz
  • Albert V. Smith
  • Emmi Tikkanen
  • Andre Uitterlinden
  • Xueli Yang
  • Weihua Zhang
  • Wei Zhao
  • Mariza de Andrade
  • Paul S. de Vries
  • Natalie R. van Zuydam
  • Sonia S. Anand
  • Lars Bertram
  • Frank Beutner
  • George Dedoussis
  • Philippe Frossard
  • Dominique Gauguier
  • Alison H. Goodall
  • Omri Gottesman
  • Marc Haber
  • Bok-Ghee Han
  • Jianfeng Huang
  • Shapour Jalilzadeh
  • Thorsten Kessler
  • Inke R. Koenig
  • Lars Lannfelt
  • Wolfgang Lieb
  • Lars Lind
  • Cecilia M. Lindgren
  • Marja-Liisa Lokki
  • Patrik K. Magnusson
  • Nadeem H. Mallick
  • Narinder Mehra
  • Thomas Meitinger
  • Fazal-ur-Rehman Memon
  • Andrew P. Morris
  • Markku S. Nieminen
  • Nancy L. Pedersen
  • Annette Peters
  • Loukianos S. Rallidis
  • Asif Rasheed
  • Maria Samuel
  • Svati H. Shah
  • Juha Sinisalo
  • Kathleen E. Stirrups
  • Stella Trompet
  • Laiyuan Wang
  • Khan S. Zaman
  • Diego Ardissino
  • Eric Boerwinkle
  • Ingrid B. Borecki
  • Erwin P. Bottinger
  • Julie E. Buring
  • John C. Chambers
  • Rory Collins
  • L. Adrienne Cupples
  • John Danesh
  • Ilja Demuth
  • Roberto Elosua
  • Stephen E. Epstein
  • Tonu Esko
  • Mary F. Feitosa
  • Oscar H. Franco
  • Maria Grazia Franzosi
  • Christopher B. Granger
  • Dongfeng Gu
  • Vilmundur Gudnason
  • Alistair S. Hall
  • Anders Hamsten
  • Tamara B. Harris
  • Stanley L. Hazen
  • Christian Hengstenberg
  • Albert Hofman
  • Erik Ingelsson
  • Carlos Iribarren
  • J. Wouter Jukema
  • Pekka J. Karhunen
  • Bong-Jo Kim
  • Jaspal S. Kooner
  • Iftikhar J. Kullo
  • Terho Lehtimaki
  • Ruth J. F. Loos
  • Olle Melander
  • Andres Metspalu
  • Winfried Maerz
  • Colin N. Palmer
  • Markus Perola
  • Thomas Quertermous
  • Daniel J. Rader
  • Paul M. Ridker
  • Samuli Ripatti
  • Robert Roberts
  • Veikko Salomaa
  • Dharambir K. Sanghera
  • Stephen M. Schwartz
  • Udo Seedorf
  • Alexandre F. Stewart
  • David J. Stott
  • Joachim Thiery
  • Pierre A. Zalloua
  • Christopher J. O'Donnell
  • Muredach P. Reilly
  • Themistocles L. Assimes
  • John R. Thompson
  • Jeanette Erdmann
  • Robert Clarke
  • Hugh Watkins
  • Sekar Kathiresan
  • Ruth McPherson
  • Panos Deloukas
  • Heribert Schunkert
  • Nilesh J. Samani
  • Martin Farrall

Summary, in English

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.

Department/s

  • Cardiovascular Research - Hypertension
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2015

Language

English

Pages

1121-1121

Publication/Series

Nature Genetics

Volume

47

Issue

10

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics
  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 1546-1718