A Genome-Wide Association Scan of RR and QT Interval Duration in 3 European Genetically Isolated Populations The EUROSPAN Project
Fabio Marroni, PhD ;
Arne Pfeufer, MD, MSc ;
Yurii S. Aulchenko, PhD ;
Christopher S. Franklin, BSc ;
Aaron Isaacs, PhD ;
Irene Pichler, PhD ;
Sarah H. Wild, MBBChir ;
Ben A. Oostra, PhD ;
Alan F. Wright, PhD ;
Harry Campbell, PhD ;
Jacqueline C. Witteman, PhD ;
Stefan Kääb, MD ;
Andrew A. Hicks, PhD ;
Ulf Gyllensten, PhD ;
Igor Rudan, MD ;
Thomas Meitinger, MD ;
Cristian Pattaro, PhD ;
Cornelia M. van Duijn, PhD ;
James F. Wilson, DPhil ;
Peter P. Pramstaller, MD on behalf of the EUROSPAN Consortium
From the Institute of Genetic Medicine (F.M., I.P., A.A.H., C.P., P.P.P.), European Academy, Bolzano, Italy; Institute of Human Genetics (A.P., T.M.), Technical University of Munich, Munich, Germany; Institute of Human Genetics (A.P., T.M.), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Munich, Germany; Genetic Epidemiology Unit (Y.S.A., A.I., B.A.O., J.C.W., C.M.v.D.), Department of Epidemiology and Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands; Centre for Population Health Sciences (C.S.F., S.H.W., H.C., I.R., J.F.W.), University of Edinburgh, Teviot Place, Edinburgh, Scotland; MRC Human Genetics Unit (A.F.W.), Western General Hospital, Edinburgh, Scotland; Medizinische Klinik I (S.K.), LMU University Clinics Grosshadern, Munich, Germany; Department of Genetics and Pathology (U.G.), Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; Croatian Centre for Global Health (I.R.), University of Split Medical School, Split, Croatia; Department of Neurology (P.P.P.), Central Hospital, Bolzano, Italy; and Department of Neurology (P.P.P.), University of Lübeck, Lübeck, Germany. F. Marroni is currently at the Institute of Applied Genomics, Parco Scientifico e Tecnologico L. Danieli, Udine, Italy.
Correspondence to Peter Pramstaller, MD, European Academy, Viale Druso/Drususallee 1, 39100 Bolzano/Bozen, Italy. E-mail peter.pramstaller{at}eurac.edu
Received November 21, 2008; accepted April 13, 2009.
Background— We set out to identify common genetic determinants of the length of the RR and QT intervals in 2325 individuals from isolated European populations.
Methods and Results— We analyzed the heart rate at rest, measured as the RR interval, and the length of the corrected QT interval for association with 318 237 single-nucleotide polymorphisms. The RR interval was associated with common variants within GPR133 , a G-protein–coupled receptor (rs885389 , P =3.9 x 10 –8 ). The QT interval was associated with the earlier reported NOS1AP gene (rs2880058, P =2.00 x 10 –10 ) and with a region on chromosome 13 (rs2478333, P =4.34 x 10 –8 ), which is 100 kb from the closest known transcript LOC730174 and has previously not been associated with the length of the QT interval.
Conclusion— Our results suggested an association between the RR interval and GPR133 and confirmed an association between the QT interval and NOS1AP .
Key Words: genetics • heart rate • population
 
CLINICAL PERSPECTIVE
The online-only Data Supplement is available at http://circgenetics.ahajournals.org/cgi/content/full/CIRCGENETICS.108.833806/DC1.
Home | Subscriptions | Archives | Feedback | Authors | Help | Circulation Journals Home | AHA Journals Home | Search
Copyright © 2009 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.
var _rsCI="us-lippincott";
var _rsCG="0";
var _rsDN="//secure-us.imrworldwide.com/";
var _rsSE=1;
var _rsS...

A Genome-Wide Association Scan of RR and QT Interval Duration in 3 European Genetically Isolated Populations: The EUROSPAN Project

10.1161/CIRCGENETICS.108.833806