Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Paul Franks

Paul Franks

Principal investigator

Paul Franks

Analysis with the exome array identifies multiple new independent variants in lipid loci

Author

  • Stavroula Kanoni
  • Nicholas G D Masca
  • Kathleen E. Stirrups
  • Tibor V. Varga
  • Helen R Warren
  • Robert A. Scott
  • Lorraine Southam
  • Weihua Zhang
  • Hanieh Yaghootkar
  • Martina Müller-Nurasyid
  • Alexessander Couto Alves
  • Rona J. Strawbridge
  • Lazaros Lataniotis
  • Nikman An Hashim
  • Céline Besse
  • Anne Boland
  • Peter S. Braund
  • John M. Connell
  • Anna Dominiczak
  • Aliki-Eleni Farmaki
  • Stephen Franks
  • Harald Grallert
  • Jan-Håkan Jansson
  • Maria Karaleftheri
  • Sirkka Keinänen-Kiukaanniemi
  • Angela Matchan
  • Dorota Pasko
  • Annette Peters
  • Neil Poulter
  • Nigel W. Rayner
  • Frida Renström
  • Olov Rolandsson
  • Maria Sabater-Lleal
  • Bengt Sennblad
  • Peter Sever
  • Denis C Shields
  • Angela Silveira
  • Alice V Stanton
  • Konstantin Strauch
  • Maciej Tomaszewski
  • Emmanouil Tsafantakis
  • Melanie Waldenberger
  • Alexandra I. F. Blakemore
  • George Dedoussis
  • Stefan A Escher
  • Jaspal S Kooner
  • Mark I. McCarthy
  • Colin N. A. Palmer
  • Anders Hamsten
  • Mark J. Caulfield
  • Timothy M. Frayling
  • Martin D Tobin
  • Marjo Riitta Jarvelin
  • Eleftheria Zeggini
  • Christian Gieger
  • John C Chambers
  • Nick J. Wareham
  • Patricia B. Munroe
  • Paul W. Franks
  • Nilesh J. Samani
  • Panos Deloukas

Summary, in English

It has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (<1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were > 1000-fold more significant than the previous sentinel variant and not in close LD (six had MAF < 5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 2.5-fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.

Department/s

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

Publishing year

2016

Language

English

Pages

4094-4106

Publication/Series

Human Molecular Genetics

Volume

25

Issue

18

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Medical Genetics

Status

Published

Research group

  • Genetic and Molecular Epidemiology

ISBN/ISSN/Other

  • ISSN: 0964-6906