Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation. / Weng, Lu Chen; Hall, Amelia Weber; Choi, Seung Hoan; Jurgens, Sean J.; Haessler, Jeffrey; Bihlmeyer, Nathan A.; Grarup, Niels; Lin, Honghuang; Teumer, Alexander; Li-Gao, Ruifang; Yao, Jie; Guo, Xiuqing; Brody, Jennifer A.; Müller-Nurasyid, Martina; Schramm, Katharina; Verweij, Niek; van den Berg, Marten E.; van Setten, Jessica; Isaacs, Aaron; Ramírez, Julia; Warren, Helen R.; Padmanabhan, Sandosh; Kors, Jan A.; de Boer, Rudolf A.; van der Meer, Peter; Sinner, Moritz F.; Waldenberger, Melanie; Psaty, Bruce M.; Taylor, Kent D.; Völker, Uwe; Kanters, Jørgen K.; Li, Man; Alonso, Alvaro; Perez, Marco V.; Vaartjes, Ilonca; Bots, Michiel L.; Huang, Paul L.; Heckbert, Susan R.; Lin, Henry J.; Kornej, Jelena; Munroe, Patricia B.; van Duijn, Cornelia M.; Asselbergs, Folkert W.; Stricker, Bruno H.; van der Harst, Pim; Kääb, Stefan; Peters, Annette; Sotoodehnia, Nona; Rotter, Jerome I.; Mook-Kanamori, Dennis O.; Dörr, Marcus; Felix, Stephan B.; Linneberg, Allan; Hansen, Torben; Arking, Dan E.; Kooperberg, Charles; Benjamin, Emelia J.; Lunetta, Kathryn L.; Ellinor, Patrick T.; Lubitz, Steven A.
I: Circulation. Genomic and precision medicine, Bind 13, Nr. 5, 2020, s. 387-395.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation
AU - Weng, Lu Chen
AU - Hall, Amelia Weber
AU - Choi, Seung Hoan
AU - Jurgens, Sean J.
AU - Haessler, Jeffrey
AU - Bihlmeyer, Nathan A.
AU - Grarup, Niels
AU - Lin, Honghuang
AU - Teumer, Alexander
AU - Li-Gao, Ruifang
AU - Yao, Jie
AU - Guo, Xiuqing
AU - Brody, Jennifer A.
AU - Müller-Nurasyid, Martina
AU - Schramm, Katharina
AU - Verweij, Niek
AU - van den Berg, Marten E.
AU - van Setten, Jessica
AU - Isaacs, Aaron
AU - Ramírez, Julia
AU - Warren, Helen R.
AU - Padmanabhan, Sandosh
AU - Kors, Jan A.
AU - de Boer, Rudolf A.
AU - van der Meer, Peter
AU - Sinner, Moritz F.
AU - Waldenberger, Melanie
AU - Psaty, Bruce M.
AU - Taylor, Kent D.
AU - Völker, Uwe
AU - Kanters, Jørgen K.
AU - Li, Man
AU - Alonso, Alvaro
AU - Perez, Marco V.
AU - Vaartjes, Ilonca
AU - Bots, Michiel L.
AU - Huang, Paul L.
AU - Heckbert, Susan R.
AU - Lin, Henry J.
AU - Kornej, Jelena
AU - Munroe, Patricia B.
AU - van Duijn, Cornelia M.
AU - Asselbergs, Folkert W.
AU - Stricker, Bruno H.
AU - van der Harst, Pim
AU - Kääb, Stefan
AU - Peters, Annette
AU - Sotoodehnia, Nona
AU - Rotter, Jerome I.
AU - Mook-Kanamori, Dennis O.
AU - Dörr, Marcus
AU - Felix, Stephan B.
AU - Linneberg, Allan
AU - Hansen, Torben
AU - Arking, Dan E.
AU - Kooperberg, Charles
AU - Benjamin, Emelia J.
AU - Lunetta, Kathryn L.
AU - Ellinor, Patrick T.
AU - Lubitz, Steven A.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - atrial fibrillation
KW - electrophysiology
KW - exome
KW - genetic
KW - genome-wide association studies
KW - population
U2 - 10.1161/CIRCGEN.119.002874
DO - 10.1161/CIRCGEN.119.002874
M3 - Journal article
C2 - 32822252
AN - SCOPUS:85094219796
VL - 13
SP - 387
EP - 395
JO - Circulation. Genomic and precision medicine
JF - Circulation. Genomic and precision medicine
SN - 2574-8300
IS - 5
ER -
ID: 251579122