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Open Access Green as soon as Postprint is submitted to ZB.
Lack of replication in polymorphisms reported to be associated with atrial fibrillation.
Heart Rhythm 8, 403-409 (2011)
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. 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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Atrial fibrillation; Arrhythmia; Genetics; Single nucleotide polymorphism; Replication; Meta-analysis
Language
english
Publication Year
2011
Prepublished in Year
2010
HGF-reported in Year
2010
ISSN (print) / ISBN
1547-5271
e-ISSN
1556-3871
Journal
Heart Rhythm
Quellenangaben
Volume: 8,
Issue: 3,
Pages: 403-409
Publisher
Elsevier
Reviewing status
Peer reviewed
Institute(s)
Institute of Biological and Medical Imaging (IBMI)
Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)
POF-Topic(s)
30205 - Bioengineering and Digital Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
Research field(s)
Enabling and Novel Technologies
Genetics and Epidemiology
Genetics and Epidemiology
PSP Element(s)
G-505500-003
G-500700-001
G-503900-005
G-504090-001
G-500700-001
G-503900-005
G-504090-001
PubMed ID
21056700
Erfassungsdatum
2010-12-31