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Kääb, S.* ; Darbar, D.* ; van Noord, C.* ; Dupuis, J.* ; Pfeufer, A. ; Newton-Cheh, C.* ; Schnabel, R. ; Makino, S.* ; Sinner, M.F.* ; Kannankeril, P.J.* ; Beckmann, B.M.* ; Choudry, S.* ; Donahue, B.S.* ; Heeringa, J.* ; Perz, S. ; Lunetta, K.L.* ; Larson, M.G.* ; Levy, D.* ; MacRae, C.A.* ; Ruskin, J.N.* ; Wacker, A.* ; Schömig, A.* ; Wichmann, H.-E. ; Steinbeck, G.* ; Meitinger, T. ; Uitterlinden, A.G.* ; Witteman, J.C.M.* ; Roden, D.M.* ; Benjamin, E.J.* ; Ellinor, P.T.*

Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation.

Eur. Heart J. 30, 813-819 (2009)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
A recent genome-wide association study identified a haplotype block on chromosome 4q25 associated with atrial fibrillation (AF). We sought to replicate this association in four independent cohorts. The Framingham Heart Study and Rotterdam Study are community-based longitudinal studies. The Vanderbilt AF Registry and German AF Network (AFNet) are case-control studies. Participants with AF (n = 3508) were more likely to be male and were older than referent participants (n = 12 173; Framingham 82 +/- 10 vs. 71 +/- 13 years; Rotterdam 73 +/- 8 vs. 69 +/- 9 years; Vanderbilt 54 +/- 14 vs. 57 +/- 14 years; AFNet 62 +/- 12 vs. 49 +/- 14 years). Single nucleotide polymorphism (SNP) rs2200733 was associated with AF in all four cohorts, with odds ratios (ORs) ranging from 1.37 in Rotterdam [95% confidence interval (CI) 1.18-1.59; P = 3.1 x 10(-5)] to 2.52 in AFNet (95% CI 2.22-2.8; P = 1.8 x 10(-49)). There also was a significant association between AF and rs10033464 in Framingham (OR 1.34; 95% CI 1.03-1.75; P = 0.031) and AFNet (OR 1.30; 95% CI 1.13-1.51; P = 0.0002), but not Vanderbilt (OR 1.16; 95% CI 0.86-1.56; P = 0.33). A meta-analysis of the current and prior AF studies revealed an OR of 1.90 (95% CI 1.60-2.26; P = 3.3 x 10(-13)) for rs2200733 and of 1.36 (95% CI 1.26-1.47; P = 6.7 x 10(-15)) for rs10033464. The non-coding SNPs rs2200733 and rs10033464 are strongly associated with AF in four cohorts of European descent. These results confirm the significant relations between AF and intergenic variants on chromosome 4.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Atrial fibrillation; Genetics; Arrhythmia; Polymorphism; Meta-analysis; of-function mutation; familial aggregation; risk-factors; population; heart; prevalence; pitx2; locus; identification; polymorphism
Sprache
Veröffentlichungsjahr 2009
HGF-Berichtsjahr 2009
ISSN (print) / ISBN 0195-668X
e-ISSN 1522-9645
Zeitschrift European Heart Journal
Quellenangaben Band: 30, Heft: 7, Seiten: 813-819 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)
Institute of Biological and Medical Imaging (IBMI)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30503 - Chronic Diseases of the Lung and Allergies
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e) G-500700-001
G-503900-001
G-505500-003
G-503900-004
DOI 10.1093/eurheartj/ehn578
Scopus ID 64849095095
PubMed ID 19141561
Erfassungsdatum 2009-07-09
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