This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 2/4/322    most recent CIRCGENETICS.108.833806v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Marroni, F. Search for Related Content PubMed PubMed Citation Articles by Marroni, F. Related Collections Clinical genetics Genomics

Original Articles

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=3.9x10^–8). The QT interval was associated with the earlier reported NOS1AP gene (rs2880058, P=2.00x10^–10) and with a region on chromosome 13 (rs2478333, P=4.34x10^–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.