Fifteen Genetic Loci Associated With the Electrocardiographic P Wave

被引：39

作者：

Christophersen, Ingrid E. ^{[1
,2
,3
,4
]}

Magnani, Jared W. ^{[5
,6
,7
]}

Yin, Xiaoyan ^{[7
]}

Barnard, John ^{[10
,11
,12
]}

Weng, Lu-Chen ^{[1
,2
,3
]}

Arking, Dan E. ^{[13
]}

Niemeijer, Maartje N. ^{[14
]}

Lubitz, Steven A. ^{[1
,2
,3
]}

Avery, Christy L. ^{[19
]}

Duan, Qing ^{[20
]}

Felix, Stephan B. ^{[26
,27
]}

Bis, Joshua C. ^{[31
]}

Kerr, Kathleen F. ^{[32
]}

Isaacs, Aaron ^{[15
,18
]}

Mueller-Nurasyid, Martina ^{[38
,42
,43
]}

Mueller, Christian ^{[44
,45
]}

North, Kari E. ^{[21
]}

Reiner, Alex P. ^{[33
,34
]}

Tinker, Lesley F. ^{[34
]}

Kors, Jan A. ^{[16
]}

Teumer, Alexander ^{[28
]}

Petersmann, Astrid ^{[29
]}

Sinner, Moritz F. ^{[42
,43
]}

Buzkova, Petra ^{[32
]}

Smith, Jonathan D. ^{[10
,11
,12
]}

Van Wagoner, David R. ^{[10
,11
,12
]}

Voelker, Uwe ^{[26
,30
]}

Waldenberger, Melanie ^{[39
,40
,43
]}

Peters, Annette ^{[40
,43
,46
]}

Meitinger, Thomas ^{[41
,43
,47
]}

Limacher, Marian C. ^{[48
]}

Wilhelmsen, Kirk C. ^{[19
,20
,22
]}

Psaty, Bruce M. ^{[31
,33
,35
,36
,49
]}

Hofman, Albert ^{[14
]}

Uitterlinden, Andre ^{[14
,17
]}

Krijthe, Bouwe P. ^{[14
]}

Zhang, Zhu-Ming ^{[50
]}

Schnabel, Renate B. ^{[44
,45
]}

Kaeaeb, Stefan ^{[42
,43
]}

van Duijn, Cornelia ^{[15
]}

Rotter, Jerome I. ^{[51
,52
]}

Sotoodehnia, Nona ^{[31
,37
]}

Doerr, Marcus ^{[26
,27
]}

Li, Yun ^{[19
,20
,23
,24
]}

Chung, Mina K. ^{[10
,11
,12
]}

Soliman, Elsayed Z. ^{[50
]}

Alonso, Alvaro ^{[53
]}

Whitsel, Eric A. ^{[25
]}

Stricker, Bruno H. ^{[14
,17
]}

Benjamin, Emelia J. ^{[5
,6
,7
,8
,9
]}

机构：

[1] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA

[2] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA

[3] MIT, Cambridge, MA USA

[4] Vestre Viken Hosp Trust, Baerum Hosp, Dept Med Res, Rud, Norway

[5] Boston Univ, Sch Med, Dept Med, Boston, MA 02215 USA

[6] Univ Pittsburgh, Med Ctr, Inst Heart & Vasc, Div Cardiol,Dept Med, Pittsburgh, PA USA

[7] Boston Univ Framingham Heart Study, Framingham, MA USA

[8] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA

[9] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA

[10] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA

[11] Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA

[12] Cleveland Clin, Dept Mol Cardiol & Quantitat Hlth Sci, Cleveland, OH 44106 USA

[13] Johns Hopkins Univ, Sch Med, Nathans Inst Genet Med, Baltimore, MD USA

[14] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands

[15] Erasmus Univ, Med Ctr, Genet Epidemiol Unit, Dept Epidemiol, Rotterdam, Netherlands

[16] Erasmus Univ, Med Ctr, Dept Med Informat, Rotterdam, Netherlands

[17] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands

[18] Maastricht Univ, Dept Biochem, Maastricht Ctr Syst Biol MaCSBio, CARIM Sch Cardiovasc Dis, Maastricht, Netherlands

[19] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA

[20] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[21] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA

[22] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA

[23] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA

[24] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC USA

[25] Univ N Carolina, Dept Med, Chapel Hill, NC USA

[26] DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany

[27] Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany

[28] Univ Med Greifswald, Inst Community Med, Greifswald, Germany

[29] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany

[30] Univ Med Greifswald, Interfaculty Inst Genet & Funct Genom, Dept Funct Gen, Greifswald, Germany

[31] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[32] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[33] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[34] Univ Washington, Hutchinson Canc Res Ctr, Seattle, WA 98195 USA

[35] Univ Washington, Cardiovascular Hlth Res Unit, Seattle, WA 98195 USA

[36] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA

[37] Univ Washington, Cardiol Div, Seattle, WA 98195 USA

[38] Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany

[39] Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, Neuherberg, Germany

[40] Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany

[41] Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Human Genet, Neuherberg, Germany

[42] Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Dept Med 1, Munich, Germany

[43] German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany

[44] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany

[45] German Ctr Cardiovasc Res DZHK eV, Partner Site Hamburg Lubeck Kiel, Munich, Germany

[46] German Ctr Diabet Res, Neuherberg, Germany

[47] Tech Univ Munich, Inst Human Genet, Munich, Germany

[48] Univ Florida, Dept Med, Div Cardiovasc Med, Gainesville, FL USA

[49] Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA

[50] Wake Forest Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC USA

来源：

CIRCULATION-CARDIOVASCULAR GENETICS | 2017年 / 10卷 / 04期

关键词：

arrhythmia; atrial function; electrocardiography; genetic variation; genome-wide association study; GENOME-WIDE ASSOCIATION; MYOSIN HEAVY-CHAIN; DOMAIN PROTEIN-1 EPAS1; ATRIAL-FIBRILLATION; ATHEROSCLEROSIS RISK; COMMON VARIANTS; HEART-RATE; SARCOPLASMIC-RETICULUM; AFRICAN-AMERICANS; CANDIDATE GENES;

D O I：

10.1161/CIRCGENETICS.116.001667

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background-The P wave on an ECG is a measure of atrial electric function, and its characteristics may serve as predictors for atrial arrhythmias. Increased mean P-wave duration and P-wave terminal force traditionally have been used as markers for left atrial enlargement, and both have been associated with increased risk of atrial fibrillation. Here, we explore the genetic basis of P-wave morphology through meta-analysis of genome-wide association study results for P-wave duration and P-wave terminal force from 12 cohort studies. Methods and Results-We included 44 456 individuals, of which 6778 (16%) were of African ancestry. Genotyping, imputation, and genome-wide association study were performed at each study site. Summary-level results were meta-analyzed centrally using inverse-variance weighting. In meta-analyses of P-wave duration, we identified 6 significant (P<5x10(-8)) novel loci and replicated a prior association with SCN10A. We identified 3 loci at SCN5A, TBX5, and CAV1/CAV2 that were jointly associated with the PR interval, PR segment, and P-wave duration. We identified 6 novel loci in meta-analysis of P-wave terminal force. Four of the identified genetic loci were significantly associated with gene expression in 329 left atrial samples. Finally, we observed that some of the loci associated with the P wave were linked to overall atrial conduction, whereas others identified distinct phases of atrial conduction. Conclusions-We have identified 6 novel genetic loci associated with P-wave duration and 6 novel loci associated with P-wave terminal force. Future studies of these loci may aid in identifying new targets for drugs that may modify atrial conduction or treat atrial arrhythmias.

引用

页数：57

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