Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation.

TitleGenetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation.
Publication TypeJournal Article
Year of Publication2020
AuthorsWeng L-C, Hall AWeber, Choi SHoan, Jurgens SJ, Haessler J, Bihlmeyer NA, Grarup N, Lin H, Teumer A, Li-Gao R, Yao J, Guo X, Brody JA, Müller-Nurasyid M, Schramm K, Verweij N, van den Berg ME, van Setten J, Isaacs A, Ramirez J, Warren HR, Padmanabhan S, Kors JA, de Boer RA, van der Meer P, Sinner MF, Waldenberger M, Psaty BM, Taylor KD, Völker U, Kanters JK, Li M, Alonso A, Perez MV, Vaartjes I, Bots ML, Huang PL, Heckbert SR, Lin HJ, Kornej J, Munroe PB, van Duijn CM, Asselbergs FW, Stricker BH, van der Harst P, Kääb S, Peters A, Sotoodehnia N, Rotter JI, Mook-Kanamori DO, Dörr M, Felix SB, Linneberg A, Hansen T, Arking DE, Kooperberg C, Benjamin EJ, Lunetta KL, Ellinor PT
Secondary AuthorsLubitz SA
JournalCirc Genom Precis Med
Volume13
Issue5
Pagination387-395
Date Published2020 Oct
ISSN2574-8300
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 (, , , , , , , ). The top variants at known sarcomere genes () were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, and ) 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.

DOI10.1161/CIRCGEN.119.002874
Alternate JournalCirc Genom Precis Med
PubMed ID32822252
PubMed Central IDPMC7578098
Grant ListR01 HL139731 / HL / NHLBI NIH HHS / United States
T32 GM007814 / GM / NIGMS NIH HHS / United States
K24 HL105780 / HL / NHLBI NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
16EIA26410001 / AHA / American Heart Association-American Stroke Association / United States
R01 HL128914 / HL / NHLBI NIH HHS / United States
K24 HL148521 / HL / NHLBI NIH HHS / United States
75N92019D00031 / HL / NHLBI NIH HHS / United States
R01 HL141989 / HL / NHLBI NIH HHS / United States
R01 HL111089 / HL / NHLBI NIH HHS / United States
R01 HL116747 / HL / NHLBI NIH HHS / United States