Multi-ancestry GWAS of the electrocardiographic PR interval identifies 210 loci underlying cardiac conduction

Published on Jul 30, 2019in bioRxiv
· DOI :10.1101/712398
Ioanna Ntalla28
Estimated H-index: 28
(QMUL: Queen Mary University of London),
Lu-Chen Weng17
Estimated H-index: 17
(Harvard University)
+ 184 AuthorsPatricia B. Munroe74
Estimated H-index: 74
(QMUL: Queen Mary University of London)
The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. We performed multi-ancestry (N=293,051) and European only (N=271,570) genome-wide association (GWAS) meta-analyses for the PR interval, discovering 210 loci of which 149 are novel. Variants at all loci nearly doubled the percentage of heritability explained, from 33.5% to 62.6%. We observed enrichment for genes involved in cardiac muscle development/contraction and the cytoskeleton highlighting key regulation processes for atrioventricular conduction. Additionally, 19 novel loci harbour genes underlying inherited monogenic heart diseases suggesting the role of these genes in cardiovascular pathology in the general population. We showed that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease risk, including distal conduction disease, AF, atrioventricular pre-excitation, non-ischemic cardiomyopathy, and coronary heart disease. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.
Figures & Tables
  • References (61)
  • Citations (0)
#1Valentina Iotchkova (EMBL-EBI: European Bioinformatics Institute)H-Index: 12
#2Ritchie Grs. (EMBL-EBI: European Bioinformatics Institute)H-Index: 2
Last.Nicole Soranzo (University of Cambridge)H-Index: 100
view all 10 authors...
#1Annalisa Buniello (EMBL-EBI: European Bioinformatics Institute)H-Index: 3
#2Jacqueline A. L. MacArthur (EMBL-EBI: European Bioinformatics Institute)H-Index: 7
Last.Helen Parkinson (EMBL-EBI: European Bioinformatics Institute)H-Index: 50
view all 24 authors...
#1Alvaro N. Barbeira (U of C: University of Chicago)H-Index: 8
#2Scott P. Dickinson (U of C: University of Chicago)H-Index: 6
Last.Hae Kyung Im (U of C: University of Chicago)H-Index: 24
view all 245 authors...
#1Jessica van Setten (UU: Utrecht University)H-Index: 22
#2Jennifer A. Brody (UW: University of Washington)H-Index: 30
Last.Nona Sotoodehnia (UW: University of Washington)H-Index: 47
view all 126 authors...
#1Carolina Roselli (Broad Institute)H-Index: 11
#2Mark Chaffin (Broad Institute)H-Index: 12
Last.Patrick T. Ellinor (Broad Institute)H-Index: 72
view all 218 authors...
#1Honghuang Lin (BU: Boston University)H-Index: 34
#2Jessica van Setten (BU: Boston University)H-Index: 2
Last.Aaron Isaacs (BU: Boston University)H-Index: 66
view all 101 authors...
#1Y Liu (Peking Union Medical College)H-Index: 7
#2Honghong Zhou (Peking Union Medical College)H-Index: 4
Last.Zhi-HuaLiu (Peking Union Medical College)H-Index: 23
view all 7 authors...
Cited By0
View next paperMolecular genetics of atrial fibrillation