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Meta-Analysis
. 2012 Apr 29;44(6):670-5.
doi: 10.1038/ng.2261.

Meta-analysis identifies six new susceptibility loci for atrial fibrillation

Patrick T Ellinor  1 , Kathryn L Lunetta, Christine M Albert, Nicole L Glazer, Marylyn D Ritchie, Albert V Smith, Dan E Arking, Martina Müller-Nurasyid, Bouwe P Krijthe, Steven A Lubitz, Joshua C Bis, Mina K Chung, Marcus Dörr, Kouichi Ozaki, Jason D Roberts, J Gustav Smith, Arne Pfeufer, Moritz F Sinner, Kurt Lohman, Jingzhong Ding, Nicholas L Smith, Jonathan D Smith, Michiel Rienstra, Kenneth M Rice, David R Van Wagoner, Jared W Magnani, Reza Wakili, Sebastian Clauss, Jerome I Rotter, Gerhard Steinbeck, Lenore J Launer, Robert W Davies, Matthew Borkovich, Tamara B Harris, Honghuang Lin, Uwe Völker, Henry Völzke, David J Milan, Albert Hofman, Eric Boerwinkle, Lin Y Chen, Elsayed Z Soliman, Benjamin F Voight, Guo Li, Aravinda Chakravarti, Michiaki Kubo, Usha B Tedrow, Lynda M Rose, Paul M Ridker, David Conen, Tatsuhiko Tsunoda, Tetsushi Furukawa, Nona Sotoodehnia, Siyan Xu, Naoyuki Kamatani, Daniel Levy, Yusuke Nakamura, Babar Parvez, Saagar Mahida, Karen L Furie, Jonathan Rosand, Raafia Muhammad, Bruce M Psaty, Thomas Meitinger, Siegfried Perz, H-Erich Wichmann, Jacqueline C M Witteman, W H Linda Kao, Sekar Kathiresan, Dan M Roden, Andre G Uitterlinden, Fernando Rivadeneira, Barbara McKnight, Marketa Sjögren, Anne B Newman, Yongmei Liu, Michael H Gollob, Olle Melander, Toshihiro Tanaka, Bruno H Ch Stricker, Stephan B Felix, Alvaro Alonso, Dawood Darbar, John Barnard, Daniel I Chasman, Susan R Heckbert, Emelia J Benjamin, Vilmundur Gudnason, Stefan Kääb
Affiliations
Meta-Analysis

Meta-analysis identifies six new susceptibility loci for atrial fibrillation

Patrick T Ellinor et al. Nat Genet. .

Abstract

Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 × 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.

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Figures

Figure 1
Figure 1
Manhattan plot of meta-analysis results for genome-wide association with atrial fibrillation. The −log10 (P value) is plotted against the physical position of each SNP on each chromosome. The threshold for genome-wide significance, P < 5 × 10−8, is indicated by the dashed line. The three previously reported loci for atrial fibrillation are indicated in blue, and the seven new loci that exceeded the genome-wide significance threshold are indicated in orange.
Figure 2
Figure 2
Regional plots for seven new atrial fibrillation loci in the discovery sample with P < 1 × 10−8. SNPs are plotted by meta-analysis P value and genomic position (NCBI Build 36). The SNP of interest is labeled. The strength of LD is indicated by red coloring. Estimated recombination rates are shown by the blue peaks, and gene annotations are indicated by dark green arrows. LD and recombination rates are based on the Utah residents of Northern and Western European ancestry (CEU) HapMap cohort (release 22). Plots were prepared using SNAP.
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