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Weng, L.C.* ; Hall, A.W.* ; Choi, S.H.* ; Jurgens, S.J.* ; Haessler, J.* ; Bihlmeyer, N.A.* ; Grarup, N.* ; Lin, H.* ; Teumer, A.* ; Li-Gao, R.* ; Yao, J.* ; Guo, X.* ; Brody, J.A.* ; Müller-Nurasyid, M. ; Schramm, K. ; Verweij, N.* ; van den Berg, M.E.* ; van Setten, J.* ; Isaacs, A.* ; Ramírez, J.* ; Warren, H.R.* ; Padmanabhan, S.* ; Kors, J.A.* ; de Boer, R.A.* ; van der Meer, P.* ; Sinner, M.F.* ; Waldenberger, M. ; Psaty, B.M.* ; Taylor, K.D.* ; Völker, U.* ; Kanters, J.K.* ; Li, M.* ; Alonso, A.* ; Perez, M.V.* ; Vaartjes, I.* ; Bots, M.L.* ; Huang, P.L.* ; Heckbert, S.R.* ; Lin, H.J.* ; Kornej, J.* ; Munroe, P.B.* ; van Duijn, C.M.* ; Asselbergs, F.W.* ; Stricker, B.H.* ; van der Harst, P.* ; Kääb, S.* ; Peters, A. ; Sotoodehnia, N.* ; Rotter, J.I.* ; Mook-Kanamori, D.O.* ; Dörr, M.* ; Felix, S.B.* ; Linneberg, A.* ; Hansen, T.* ; Arking, D.E.* ; Kooperberg, C.* ; Benjamin, E.J.* ; Lunetta, K.L.* ; Ellinor, P.T.* ; Lubitz, S.A.*

Genetic determinants of electrocardiographic P-wave duration and relation to atrial fibrillation.

Circ. Genom. Precis. Med. 13, 387-395 (2020)
Postprint DOI PMC
Open Access Green
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Atrial Fibrillation ; Electrophysiology ; Exome ; Genetic ; Genome-wide Association Studies ; Population; Myosin Heavy-chain; Risk; Association; Recurrence; Expression; Indexes; Protein; Hmga2; Myh6
ISSN (print) / ISBN 2574-8300
e-ISSN 2574-8300
Journal Circulation Genomic and precision medicine
Quellenangaben Volume: 13, Issue: 5, Pages: 387-395 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Publishing Place Philadelphia, Pa.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology II (EPI2)
Grants Fondation Leducq
Medical Research Council
National, Heart, Lung and Blood Institute
AHA
National Science Foundation
National Institute of General Medical Sciences
AHA Strategically Focused Research Networks (SFRN)
People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant
European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant
American Heart Association
NIH
European Union
Laughlin Family Fund
National Institutes of Health (NIH)
American Heart Association (AHA) Postdoctoral Fellowship Award