Background
Atrial fibrillation (AF) is the most common sustained arrhythmia and has a substantial
heritable component. Numerous associations between single nucleotide polymorphisms
(SNPs) and AF have been described, but few have been replicated.
Objective
We sought to systematically replicate SNPs that are reported to be associated with
AF in two large study samples of European descent.
Methods
We searched PubMed for studies reporting associations between SNPs and AF published
before July 1, 2007. SNPs were genotyped in two independent case-control samples from
Germany and the United States. Associations between SNPs and AF were assessed using
logistic regression models adjusting for age, sex, and hypertension. A meta-analysis
of the results from the two studies was performed.
Results
We identified 21 SNPs and the angiotensin-converting enzyme insertion/deletion polymorphism
that were reported to be associated with AF in the literature. Nine of these genetic
variants were not represented on common genome-wide SNP arrays. We successfully genotyped
21 of these 22 variants in 2,145 cases with AF from the German Competence Network
for Atrial Fibrillation and 4,073 controls from the KORA S4 study and 16 variants
in 790 cases and 1,330 controls from the Massachusetts General Hospital. None of the
SNPs replicated in independent populations with AF.
Conclusion
Our results suggest that previously reported associations to AF were likely false
positives and highlight the need for systematic replication of genetic associations
in large, independent cohorts to accurately detect variants associated with disease.
Keywords
Abbreviations:
ACE I/D (angiotensin-converting enzyme insertion/deletion), AF (atrial fibrillation), AFNET (German Competence Network for Atrial Fibrillation), CI (confidence interval), GWAS (genome-wide association study), MALDI-TOF (matrix-assisted laser desorption/ionization time of flight), MGH (Massachusetts General Hospital), OR (odds ratio), SNP (single nucleotide polymorphism)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: November 09, 2010
Accepted:
November 1,
2010
Received:
January 21,
2010
Footnotes
MF Sinner, SA Lubitz, PT Ellinor, and S Kääb contributed equally to this study.
This study was funded by an LMU Research Grant FöFoLe 577/569 to Dr. Sinner; the German National Genome Research Network NGFN 01 GS 0499, 01 GS 0838, German Federal Ministry of research 01 EZ 0874, German Competence Network on AF (AFNET) 01 GI 0204/N, Leducq Foundation 07-CVD 03, and LMU Excellence Initiative to Dr. Kääb; the German National Genome Research Network NGFN 01GR0803 and the BMBF German Federal Ministry of research 01EZ0874 to Dr. Pfeufer; the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke to Dr. Ellinor; and the National Institutes of Health to Dr. Rosand (R01NS059727), Dr. Furie (5P50NS051343), Dr. Lubitz (T32HL007575), and Drs. Ellinor and Benjamin (R01HL092577). The KORA platform is funded by the BMBF and by the State of Bavaria.
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Copyright
© 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
