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Paul Franks

Paul Franks

Principal investigator

Paul Franks

Association analyses based on false discovery rate implicate new loci for coronary artery disease

Author

  • Christopher P Nelson
  • Anuj Goel
  • Adam S Butterworth
  • Stavroula Kanoni
  • Tom R. Webb
  • Eirini Marouli
  • Lingyao Zeng
  • Ioanna Ntalla
  • Florence Y. Lai
  • Jemma C Hopewell
  • Olga Giannakopoulou
  • Tao Jiang
  • Stephen E. Hamby
  • Emanuele Di Angelantonio
  • Themistocles L Assimes
  • Erwin P Bottinger
  • John C Chambers
  • Robert Clarke
  • Colin N. A. Palmer
  • Richard M. Cubbon
  • Patrick T Ellinor
  • Raili Ermel
  • Evangelos Evangelou
  • Paul W. Franks
  • Christopher Grace
  • Dongfeng Gu
  • Aroon D Hingorani
  • Joanna M. M. Howson
  • Erik Ingelsson
  • Adnan Kastrati
  • Thorsten Kessler
  • Theodosios Kyriakou
  • Terho Lehtimäki
  • Xiangfeng Lu
  • Yingchang Lu
  • Winfried März
  • Ruth McPherson
  • Andres Metspalu
  • Mar Pujades-Rodriguez
  • Arno Ruusalepp
  • Eric Schadt
  • Amand F. Schmidt
  • Michael J. Sweeting
  • Pierre A. Zalloua
  • Kamal Alghalayini
  • Bernard D. Keavney
  • Jaspal S Kooner
  • Ruth J F Loos
  • Riyaz S. Patel
  • Martin K. Rutter
  • Maciej Tomaszewski
  • Ioanna Tzoulaki
  • Eleftheria Zeggini
  • Jeanette Erdmann
  • George Dedoussis
  • Johan L M Björkegren
  • Heribert Schunkert
  • Martin Farrall
  • John Danesh
  • Nilesh J. Samani
  • Hugh Watkins
  • Panos Deloukas

Summary, in English

Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10 '8) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1,2,3,4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; n cases = 10,801) as well as a stricter definition without angina (HARD; n cases = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS. This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold, thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.

Department/s

  • Genetic and Molecular Epidemiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2017-09-01

Language

English

Pages

1385-1391

Publication/Series

Nature Genetics

Volume

49

Issue

9

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics
  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Genetic and Molecular Epidemiology

ISBN/ISSN/Other

  • ISSN: 1061-4036