Lack of replication in polymorphisms reported to be associated with atrial fibrillation.
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.


CONCLUSIONS
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.
Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Moritz F
MF
Sinner
Steven A
SA
Lubitz
Arne
A
Pfeufer
Seiko
S
Makino
Britt-Maria
BM
Beckmann
Kathryn L
KL
Lunetta
Gerhard
G
Steinbeck
Siegfried
S
Perz
Rosanna
R
Rahman
Akshata
A
Sonni
Steven M
SM
Greenberg
Karen L
KL
Furie
H-Erich
HE
Wichmann
Thomas
T
Meitinger
Annette
A
Peters
Emelia J
EJ
Benjamin
Jonathan
J
Rosand
Patrick T
PT
Ellinor
Stefan
S
Kääb
D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics*; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results