Institut for Biomedicin

Lars Bolund

Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Dokumenter

DOI

  • Anders Albrechtsen, Bioinformatics, Danmark
  • N Grarup, Danmark
  • Y Li, Danmark
  • Thomas Hempel Sparsø, Metabolics Genetics, Danmark
  • G Tian
  • ,
  • H Cao
  • ,
  • Tao Jiang, Department of Physics, Danmark
  • S Y Kim, Danmark
  • Thorfinn Sand Korneliussen, 2012 Statens Naturhistoriske Museum, Danmark
  • Q Li, Danmark
  • C Nie
  • ,
  • Rui Wu, Institut for Energiteknik, Danmark
  • Line Skotte, Risø National Laboratory for Sustainable Energy, Danmark
  • A P Morris
  • ,
  • C Ladenvall
  • ,
  • S Cauchi
  • ,
  • A Stančáková
  • ,
  • G Andersen, Danmark
  • A Astrup
  • ,
  • Karina Banasik, Afd. for Endokrinologisk Forskning, Danmark
  • A J Bennett
  • ,
  • Lars Bolund
  • G Charpentier
  • ,
  • Yingke Chen, Machine Intelligence, Danmark
  • J M Dekker
  • ,
  • A S F Doney
  • ,
  • M Dorkhan
  • ,
  • T Forsen
  • ,
  • T M Frayling
  • ,
  • C J Groves
  • ,
  • Y Gui
  • ,
  • G Hallmans
  • ,
  • A T Hattersley
  • ,
  • K He
  • ,
  • G A Hitman
  • ,
  • J Holmkvist
  • ,
  • Shaojun Huang, Institut for Energiteknik, Danmark
  • H Jiang, Danmark
  • X Jin
  • ,
  • J M Justesen, Danmark
  • K Kristiansen, Danmark
  • J Kuusisto
  • ,
  • Marianne Lajer, Division of Poultry, Fish and Fur Animals, Danmark
  • O Lantieri
  • ,
  • W Li
  • ,
  • H Liang, Danmark
  • Q Liao
  • ,
  • X Liu, Danmark
  • T Lauritzen
  • O Pedersen, Danmark
  • D.E.S.I.R. Study Group
AIMS/HYPOTHESIS: Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes. METHODS: The study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 × 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 × 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 × 10(-10)). CONCLUSIONS/INTERPRETATION: We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
OriginalsprogEngelsk
TidsskriftDiabetologia
Vol/bind56
Nummer2
Sider (fra-til)298-310
Antal sider13
ISSN0012-186X
DOI
StatusUdgivet - feb. 2013

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