| Genome-wide association study of PR interval. | |
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MedLine Citation:
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PMID: 20062060 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-analysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 x 10(-8). At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX2-5 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P < 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation. |
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Authors:
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Arne Pfeufer; Charlotte van Noord; Kristin D Marciante; Dan E Arking; Martin G Larson; Albert Vernon Smith; Kirill V Tarasov; Martina Müller; Nona Sotoodehnia; Moritz F Sinner; Germaine C Verwoert; Man Li; W H Linda Kao; Anna Köttgen; Josef Coresh; Joshua C Bis; Bruce M Psaty; Kenneth Rice; Jerome I Rotter; Fernando Rivadeneira; Albert Hofman; Jan A Kors; Bruno H C Stricker; André G Uitterlinden; Cornelia M van Duijn; Britt M Beckmann; Wiebke Sauter; Christian Gieger; Steven A Lubitz; Christopher Newton-Cheh; Thomas J Wang; Jared W Magnani; Renate B Schnabel; Mina K Chung; John Barnard; Jonathan D Smith; David R Van Wagoner; Ramachandran S Vasan; Thor Aspelund; Gudny Eiriksdottir; Tamara B Harris; Lenore J Launer; Samer S Najjar; Edward Lakatta; David Schlessinger; Manuela Uda; Gonçalo R Abecasis; Bertram Müller-Myhsok; Georg B Ehret; Eric Boerwinkle; Aravinda Chakravarti; Elsayed Z Soliman; Kathryn L Lunetta; Siegfried Perz; H-Erich Wichmann; Thomas Meitinger; Daniel Levy; Vilmundur Gudnason; Patrick T Ellinor; Serena Sanna; Stefan Kääb; Jacqueline C M Witteman; Alvaro Alonso; Emelia J Benjamin; Susan R Heckbert |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2010-01-10 |
Journal Detail:
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Title: Nature genetics Volume: 42 ISSN: 1546-1718 ISO Abbreviation: Nat. Genet. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-27 Completed Date: 2010-02-17 Revised Date: 2012-04-30 |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: United States |
Other Details:
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Languages: eng Pagination: 153-9 Citation Subset: IM |
Affiliation:
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Institute of Human Genetics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. arne.pfeufer@web.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Atrial Fibrillation / genetics, physiopathology Cohort Studies Electrocardiography* Female Genetic Loci / genetics Genetic Predisposition to Disease Genome-Wide Association Study* Heart Conduction System / physiology* Humans Male Meta-Analysis as Topic |
| Grant Support | |
ID/Acronym/Agency:
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263-MA-410953//PHS HHS; 6R01-NS-17950/NS/NINDS NIH HHS; AG-028321/AG/NIA NIH HHS; DK063491/DK/NIDDK NIH HHS; HHSN268200625226C//PHS HHS; HL-076784/HL/NHLBI NIH HHS; HL-080025/HL/NHLBI NIH HHS; K23 HL080025-05/HL/NHLBI NIH HHS; L30 HL097675-01/HL/NHLBI NIH HHS; M01 RR000425-30S1/RR/NCRR NIH HHS; M01-RR-00425/RR/NCRR NIH HHS; N01 AG012100/AG/NIA NIH HHS; N01 AG012109/AG/NIA NIH HHS; N01 HC015103/HC/NHLBI NIH HHS; N01 HC025195/HC/NHLBI NIH HHS; N01 HC035129/HC/NHLBI NIH HHS; N01 HC045133/HC/NHLBI NIH HHS; N01 HC055015/HC/NHLBI NIH HHS; N01 HC055016/HC/NHLBI NIH HHS; N01 HC055018/HC/NHLBI NIH HHS; N01 HC055019/HC/NHLBI NIH HHS; N01 HC055020/HC/NHLBI NIH HHS; N01 HC055021/HC/NHLBI NIH HHS; N01 HC055022/HC/NHLBI NIH HHS; N01 HC055222/HC/NHLBI NIH HHS; N01 HC075150/HC/NHLBI NIH HHS; N01 HC085079/HC/NHLBI NIH HHS; N01 HC085080/HC/NHLBI NIH HHS; N01 HC085081/HC/NHLBI NIH HHS; N01 HC085082/HC/NHLBI NIH HHS; N01 HC085083/HC/NHLBI NIH HHS; N01 HC085084/HC/NHLBI NIH HHS; N01 HC085085/HC/NHLBI NIH HHS; N01 HC085086/HC/NHLBI NIH HHS; N01-AG-1-2109/AG/NIA NIH HHS; N01-AG-12100/AG/NIA NIH HHS; N01-HC-15103/HC/NHLBI NIH HHS; N01-HC-25195/HC/NHLBI NIH HHS; N01-HC-35129/HC/NHLBI NIH HHS; N01-HC-45133/HC/NHLBI NIH HHS; N01-HC-55015/HC/NHLBI NIH HHS; N01-HC-55016/HC/NHLBI NIH HHS; N01-HC-55018/HC/NHLBI NIH HHS; N01-HC-55019/HC/NHLBI NIH HHS; N01-HC-55020/HC/NHLBI NIH HHS; N01-HC-55021/HC/NHLBI NIH HHS; N01-HC-55022/HC/NHLBI NIH HHS; N01-HC-55222/HC/NHLBI NIH HHS; N01-HC-75150/HC/NHLBI NIH HHS; N01-HC-85079/HC/NHLBI NIH HHS; N01-HC-85080/HC/NHLBI NIH HHS; N01-HC-85081/HC/NHLBI NIH HHS; N01-HC-85082/HC/NHLBI NIH HHS; N01-HC-85083/HC/NHLBI NIH HHS; N01-HC-85084/HC/NHLBI NIH HHS; N01-HC-85085/HC/NHLBI NIH HHS; N01-HC-85086/HC/NHLBI NIH HHS; N01-HC25195/HC/NHLBI NIH HHS; N02 HL64278/HL/NHLBI NIH HHS; P30 DK063491/DK/NIDDK NIH HHS; P30 DK063491-019004/DK/NIDDK NIH HHS; P30 DK063491-029004/DK/NIDDK NIH HHS; P30 DK063491-039004/DK/NIDDK NIH HHS; P30 DK063491-049004/DK/NIDDK NIH HHS; P30 DK063491-07/DK/NIDDK NIH HHS; P50 HL077107-059001/HL/NHLBI NIH HHS; P50-HL077107/HL/NHLBI NIH HHS; R01 AG028321-04/AG/NIA NIH HHS; R01 DK033651/DK/NIDDK NIH HHS; R01 DK033651-29/DK/NIDDK NIH HHS; R01 HL059367-09/HL/NHLBI NIH HHS; R01 HL076784-05/HL/NHLBI NIH HHS; R01 HL086694-03/HL/NHLBI NIH HHS; R01 HL087641-03/HL/NHLBI NIH HHS; R01 HL087652-03/HL/NHLBI NIH HHS; R01 HL088456-03/HL/NHLBI NIH HHS; R01 HL090620-01A1/HL/NHLBI NIH HHS; R01 HL090620-01A1S1/HL/NHLBI NIH HHS; R01 HL090620-01A1S2/HL/NHLBI NIH HHS; R01 HL090620-02/HL/NHLBI NIH HHS; R01 HL090620-03/HL/NHLBI NIH HHS; R01 HL090620-04/HL/NHLBI NIH HHS; R01 NS017950-28/NS/NINDS NIH HHS; R01-HL-054512/HL/NHLBI NIH HHS; R01-HL-086694/HL/NHLBI NIH HHS; R01-HL-087641/HL/NHLBI NIH HHS; R01-HL-087652/HL/NHLBI NIH HHS; R01-HL-088456/HL/NHLBI NIH HHS; R01-HL-59367/HL/NHLBI NIH HHS; R01-HL090620/HL/NHLBI NIH HHS; U01 HG004402-02/HG/NHGRI NIH HHS; U01 HL054512-13/HL/NHLBI NIH HHS; U01 HL080295-05/HL/NHLBI NIH HHS; U01-HG004402/HG/NHGRI NIH HHS; U01-HL-080295/HL/NHLBI NIH HHS; UL1 RR025005-01/RR/NCRR NIH HHS; UL1-RR025005/RR/NCRR NIH HHS |
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