Weng, L-C;
Hall, AW;
Choi, SH;
Jurgens, SJ;
Haessler, J;
Bihlmeyer, NA;
Grarup, N;
... Lubitz, SA; + view all
(2020)
Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation.
Circulation: Genomic and Precision Medicine
, 13
(5)
pp. 387-395.
10.1161/CIRCGEN.119.002874.
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Abstract
Background: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD. / Methods: Fifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. / Results: We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci (TTN, CAND2, SCN10A, PITX2, CAV1, SYNPO2L, SOX5, TBX5, MYH6, RPL3L). The top variants at known sarcomere genes (TTN, MYH6) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A) were associated with longer PWD but lower AF risk. / Conclusions: Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF.
| Type: | Article |
|---|---|
| Title: | Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1161/CIRCGEN.119.002874 |
| Publisher version: | https://doi.org/10.1161/CIRCGEN.119.002874 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | genetic, exomeatrial fibrillation, genome-wide association studies, electrophysiology, population |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10126667 |
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