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RESEARCH PRODUCT

Genome-wide association study of PR interval.

Siegfried PerzThomas J. WangThomas J. WangVilmundur GudnasonThomas MeitingerElsayed Z. SolimanEric BoerwinkleBertram Müller-myhsokMoritz F. SinnerNona SotoodehniaGonçalo R. AbecasisDan E. ArkingDaniel LevyW. H. Linda KaoRenate B. SchnabelRenate B. SchnabelJerome I. RotterStefan KääbFernando RivadeneiraDavid R. Van WagonerJoshua C. BisKirill V. TarasovGudny EiriksdottirRamachandran S. VasanRamachandran S. VasanChristopher Newton-chehDavid SchlessingerJan A. KorsJosef CoreshKristin D. MarcianteH.-erich WichmannMartina MüllerThor AspelundBruno H. StrickerAlvaro AlonsoSamer S. NajjarGermaine C. VerwoertMan LiBritt M. BeckmannJared W. MagnaniKathryn L. LunettaEdward G. LakattaSerena SannaLenore J. LaunerAlbert V. SmithEmelia J. BenjaminEmelia J. BenjaminCornelia M. Van DuijnKenneth RiceSteven A. LubitzPatrick T. EllinorArne PfeuferCharlotte Van NoordJonathan D. SmithAlbert HofmanChristian GiegerJacqueline C.m. WittemanMartin G. LarsonMartin G. LarsonManuela UdaAnna KöttgenSusan R. HeckbertAndré G. UitterlindenGeorg EhretBruce M. PsatyBruce M. PsatyJohn BarnardTamara B. HarrisWiebke SauterAravinda ChakravartiMina K. Chung

subject

MaleCandidate genePopulationvoltage gated sodium channelGenome-wide association studyLocus (genetics)030204 cardiovascular system & hematologyBiologyArticleCohort Studiesquantitative trait03 medical and health sciencesRotterdam StudyElectrocardiography0302 clinical medicineMeta-Analysis as TopicHeart Conduction SystemAtrial FibrillationGeneticsmedicineHumansGenetic Predisposition to Diseasecardiovascular diseasesPR intervaleducation030304 developmental biologyGenetic associationAgedGeneticsdevelopmental genes0303 health scienceseducation.field_of_studygenome-wide association studyPQ intervalAtrial fibrillationmedicine.diseaseGenetic Locicardiovascular systemPR intervalFemale

description

The electrocardiographic PR interval reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation (AF). To identify underlying common genetic variation, we meta-analyzed genome-wide association results for PR interval from seven community-based studies of European-ancestry individuals in the CHARGE consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N=28,517). Statistically significant loci (P<5×10-8) were tested for association with AF (N=5,741 cases). We identified nine loci associated with PR interval. At chromosome 3p22.2, we observed two independent associations in voltage gated sodium channel genes SCN10A and SCN5A, while six loci were near cardiac developmental genes CAV1/CAV2, NKX2-5 (CSX1), SOX5, WNT11, MEIS1, and TBX5/TBX3. Another signal was at ARHGAP24, a locus without known relevance to the heart. Five of the nine loci, SCN5A, SCN10A, NKX2-5, CAV1/CAV2, and SOX5, were also associated with AF (P<0.0056). Common genetic variation, particularly in ion channel and developmental genes, contributes significantly to atrial and atrioventricular conduction and to AF risk.

yearjournalcountryeditionlanguage
2009-07-16Nature genetics
10.1038/ng.517https://pubmed.ncbi.nlm.nih.gov/20062060