@article{3774587faa514aefabd39e1a64a575bf,
title = "Large scale replication and meta-analysis of variants on chromosome 4q25 associated with atrial fibrillation",
abstract = "Aims: 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.Methods and resultsThe 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 × 10 -5] to 2.52 in AFNet (95 CI 2.22-2.8; P = 1.8 × 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 × 10-13) for rs2200733 and of 1.36 (95 CI 1.26-1.47; P = 6.7 × 10-15) for rs10033464.ConclusionThe 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.",
keywords = "Arrhythmia, Atrial fibrillation, Genetics, Meta-analysis, Polymorphism",
author = "Stefan K{\"a}{\"a}b and Dawood Darbar and {Van Noord}, Charlotte and Jos{\'e}e Dupuis and Arne Pfeufer and Christopher Newton-Cheh and Renate Schnabel and Seiko Makino and Sinner, {Moritz F.} and Kannankeril, {Prince J.} and Beckmann, {Britt M.} and Subbarao Choudry and Donahue, {Brian S.} and Jan Heeringa and Siegfried Perz and Lunetta, {Kathryn L.} and Larson, {Martin G.} and Daniel Levy and MacRae, {Calum A.} and Ruskin, {Jeremy N.} and Annette Wacker and Albert Sch{\"o}mig and Wichmann, {H. Erich} and Gerhard Steinbeck and Thomas Meitinger and Uitterlinden, {Andr{\'e} G.} and Witteman, {Jacqueline C.M.} and Roden, {Dan M.} and Benjamin, {Emelia J.} and Ellinor, {Patrick T.}",
note = "Funding Information: This study was funded by grants to P.T.E. from the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke, by the German Federal Ministry of Education and Research (BMBF) in the context of the German National Genome Research Network (NGFN), the German National Competence Network on Atrial Fibrillation (AFNet), the Leducq Foundation, and the Bioinformatics for the Functional Analysis of Mammalian Genomes program (BFAM) by grants to S.K. (01GS0499, 01GI0204, and the Leducq Transatlantic Network on AF 07-CVD 03), H.-E.W. (01GI0204) and to T.M. (01GR0103). The KORA platform is funded by the BMBF and by the State of Bavaria. Supported in part by grants from the United States Public Health Service (HL075266) to D.D. and U01 (HL65962) to D.M.R. The Framingham Heart Study is funded by National Institutes of Health contract N01-HC-25195; the work was also supported in part by grants from the National Institutes of Health HL076784, AG028321, N01-HC 25195 to E.J.B. and 6R01-NS 17950 and Deutsche Forschungsgemeinschaft (German Research Foundation) Research Fellowship SCHN 1149/1-1 to R.S. C.N.-C. is supported by a K23, a Doris Duke Clinical Scientist Development Award, and a Burroughs Wellcome Fund Career Award for Medical Scientists.",
year = "2009",
month = apr,
doi = "10.1093/eurheartj/ehn578",
language = "English",
volume = "30",
pages = "813--819",
journal = "European Heart Journal",
issn = "0195-668X",
publisher = "Oxford University Press",
number = "7",
}