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

Autor:	Weng LC; Cardiovascular Research Center (L.-C.W., A.W.H., P.L.H., P.T.E.), MGH, Boston.; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA (L.-C.W., A.W.H., S.H.C., S.J.J., P.T.E., S.A.L.)., Hall AW; Cardiovascular Research Center (L.-C.W., A.W.H., P.L.H., P.T.E.), MGH, Boston.; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA (L.-C.W., A.W.H., S.H.C., S.J.J., P.T.E., S.A.L.)., Choi SH; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA (L.-C.W., A.W.H., S.H.C., S.J.J., P.T.E., S.A.L.)., Jurgens SJ; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA (L.-C.W., A.W.H., S.H.C., S.J.J., P.T.E., S.A.L.)., Haessler J; Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (J.H., C.K.)., Bihlmeyer NA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (N.A.B., D.E.A.)., Grarup N; Novo Nordisk Foundation Center for Basic Metabolic Research (N.G., T.H.), Faculty of Health & Medicine Sciences, University of Copenhagen, Denmark., Lin H; Boston University & NHLBI's Framingham Heart Study, Framingham, MA (H.L., J.K., E.J.B., K.L.L.).; Section of Computational Biomedicine, Department of Medicine (H.L.), Boston University School of Medicine, Boston, MA., Teumer A; DZHK (German Center for Cardiovascular Research), partner site Greifswald, Germany (A.T., U.V., M.D., S.B.F.).; Institute for Community Medicine (A.T.), University Medicine Greifswald, Germany., Li-Gao R; Department of Clinical Epidemiology (R.L.-G., D.O.M.-K.), Leiden University Medical Center, the Netherlands., Yao J; The Institute for Translational Genomics & Population Sciences at Harbor-UCLA Medical Center, Torrance, CA (J.Y., X.G., K.D.T., H.J.L., J.I.R.)., Guo X; The Institute for Translational Genomics & Population Sciences at Harbor-UCLA Medical Center, Torrance, CA (J.Y., X.G., K.D.T., H.J.L., J.I.R.).; Department of Pediatrics (X.G., K.D.T., H.J.L.), David Geffen School of Medicine at UCLA, Los Angeles, CA., Brody JA; Cardiovascular Health Research Unit, Department of Medicine (J.A.B., N.S.), University of Washington., Müller-Nurasyid M; Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Germany (M.M.-N., K.S.).; Department of Internal Medicine I (Cardiology), Hospital of the Ludwig-Maximilians-University (LMU) Munich, Germany (M.M.-N., K.S., M.F.S., S.K.).; Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany (M.M.-N., K.S.)., Schramm K; Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Germany (M.M.-N., K.S.).; Department of Internal Medicine I (Cardiology), Hospital of the Ludwig-Maximilians-University (LMU) Munich, Germany (M.M.-N., K.S., M.F.S., S.K.).; Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany (M.M.-N., K.S.)., Verweij N; Genomics plc, Oxford, United Kingdom (N.V.).; Department of Cardiology (N.V., R.A.d.B., P.v.d.M., P.v.d.H.), University of Groningen & University Medical Center., van den Berg ME; Department of Epidemiology (M.E.v.d.B.)., van Setten J; Erasmus MC, Medical Center Rotterdam, Division of Heart & Lungs, Department of Cardiology, University of Utrecht, University Medical Center Utrecht (J.v.S., F.W.A.)., Isaacs A; CARIM School for Cardiovascular Diseases (A.I.), Maastricht University, the Netherlands.; Department of Physiology (A.I.), Maastricht University, the Netherlands., Ramírez J; National Institute for Health Research, Barts Cardiovascular Biomedical Research Center (J.R., H.R.W., P.B.M.), Queen Mary University of London, London.; William Harvey Research Institute, Barts & The London School of Medicine & Dentistry (J.R., H.R.W., P.B.M.), Queen Mary University of London, London., Warren HR; National Institute for Health Research, Barts Cardiovascular Biomedical Research Center (J.R., H.R.W., P.B.M.), Queen Mary University of London, London.; William Harvey Research Institute, Barts & The London School of Medicine & Dentistry (J.R., H.R.W., P.B.M.), Queen Mary University of London, London., Padmanabhan S; Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, United Kingdom (S.P.)., Kors JA; Department of Medicine Informatics (J.A.K.), Erasmus University Medical Center, Rotterdam, the Netherlands., de Boer RA; Department of Cardiology (N.V., R.A.d.B., P.v.d.M., P.v.d.H.), University of Groningen & University Medical Center., van der Meer P; Department of Cardiology (N.V., R.A.d.B., P.v.d.M., P.v.d.H.), University of Groningen & University Medical Center., Sinner MF; Department of Internal Medicine I (Cardiology), Hospital of the Ludwig-Maximilians-University (LMU) Munich, Germany (M.M.-N., K.S., M.F.S., S.K.).; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance (M.F.S., M.W., S.K., A.P.)., Waldenberger M; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance (M.F.S., M.W., S.K., A.P.).; Institute of Epidemiology (M.W., A.P.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.; Research Unit of Molecular Epidemiology (M.W.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany., Psaty BM; Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology & Health Services (B.M.P.), University of Washington.; Kaiser Permanente Washington Health Research Institute, Seattle, WA (B.M.P.)., Taylor KD; The Institute for Translational Genomics & Population Sciences at Harbor-UCLA Medical Center, Torrance, CA (J.Y., X.G., K.D.T., H.J.L., J.I.R.).; Department of Pediatrics (X.G., K.D.T., H.J.L.), David Geffen School of Medicine at UCLA, Los Angeles, CA., Völker U; DZHK (German Center for Cardiovascular Research), partner site Greifswald, Germany (A.T., U.V., M.D., S.B.F.).; Interfaculty Institute for Genetics & Functional Genomics (U.V.), University Medicine Greifswald, Germany., Kanters JK; Lab of Experimental Cardiology (J.K.K.), Faculty of Health & Medicine Sciences, University of Copenhagen, Denmark., Li M; Division of Nephrology & Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT (M.L.)., Alonso A; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA (A.A.)., Perez MV; Department of Medicine, Stanford University, Palo Alto, CA (M.V.P.)., Vaartjes I; Julius Center for Health Sciences & Primary Care, University Medical Center Utrecht, Utrecht University, the Netherlands (I.V., M.L.B.)., Bots ML; Julius Center for Health Sciences & Primary Care, University Medical Center Utrecht, Utrecht University, the Netherlands (I.V., M.L.B.)., Huang PL; Cardiovascular Research Center (L.-C.W., A.W.H., P.L.H., P.T.E.), MGH, Boston., Heckbert SR; Cardiovascular Health Research Unit, Department of Epidemiology (S.R.H.), University of Washington., Lin HJ; The Institute for Translational Genomics & Population Sciences at Harbor-UCLA Medical Center, Torrance, CA (J.Y., X.G., K.D.T., H.J.L., J.I.R.).; Department of Pediatrics (X.G., K.D.T., H.J.L.), David Geffen School of Medicine at UCLA, Los Angeles, CA., Kornej J; Boston University & NHLBI's Framingham Heart Study, Framingham, MA (H.L., J.K., E.J.B., K.L.L.)., Munroe PB; National Institute for Health Research, Barts Cardiovascular Biomedical Research Center (J.R., H.R.W., P.B.M.), Queen Mary University of London, London.; William Harvey Research Institute, Barts & The London School of Medicine & Dentistry (J.R., H.R.W., P.B.M.), Queen Mary University of London, London., van Duijn CM; Department of Epidemiology (C.M.v.D.), Erasmus University Medical Center, Rotterdam, the Netherlands.; Nuffield Department of Population Health, Medical Sciences Division, St. Cross College, Oxford University (C.M.v.D.)., Asselbergs FW; Erasmus MC, Medical Center Rotterdam, Division of Heart & Lungs, Department of Cardiology, University of Utrecht, University Medical Center Utrecht (J.v.S., F.W.A.).; Health Data Research UK & Institute of Health Informatics (F.W.A.), University College London, United Kingdom.; Institute of Cardiovascular Science, Faculty of Population Health Sciences (F.W.A.), University College London, United Kingdom., Stricker BH; Department of Internal Medicine (B.H.S.).; Department of Medicine Informatics (B.H.S.).; Inspectorate of Health Care (B.H.S.), ICIN-Netherlands Heart Institute, Utrecht., van der Harst P; Department of Cardiology (N.V., R.A.d.B., P.v.d.M., P.v.d.H.), University of Groningen & University Medical Center.; Department of Genetics (P.v.d.H.), University of Groningen & University Medical Center.; Durrer Center for Cardiogenetic Research (P.v.d.H.), ICIN-Netherlands Heart Institute, Utrecht., Kääb S; Department of Internal Medicine I (Cardiology), Hospital of the Ludwig-Maximilians-University (LMU) Munich, Germany (M.M.-N., K.S., M.F.S., S.K.).; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance (M.F.S., M.W., S.K., A.P.)., Peters A; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance (M.F.S., M.W., S.K., A.P.).; Institute of Epidemiology (M.W., A.P.), Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.; German Center for Diabetes Research, Neuherberg, Germany (A.P.)., Sotoodehnia N; Cardiovascular Health Research Unit, Department of Medicine (J.A.B., N.S.), University of Washington., Rotter JI; The Institute for Translational Genomics & Population Sciences at Harbor-UCLA Medical Center, Torrance, CA (J.Y., X.G., K.D.T., H.J.L., J.I.R.).; Departments of Pediatrics & Human Genetics (J.I.R.), David Geffen School of Medicine at UCLA, Los Angeles, CA., Mook-Kanamori DO; Department of Clinical Epidemiology (R.L.-G., D.O.M.-K.), Leiden University Medical Center, the Netherlands.; Department of Public Health & Primary Care (D.O.M.-K.), Leiden University Medical Center, the Netherlands., Dörr M; DZHK (German Center for Cardiovascular Research), partner site Greifswald, Germany (A.T., U.V., M.D., S.B.F.).; Department of Internal Medicine B (M.D., S.B.F.), University Medicine Greifswald, Germany., Felix SB; DZHK (German Center for Cardiovascular Research), partner site Greifswald, Germany (A.T., U.V., M.D., S.B.F.).; Department of Internal Medicine B (M.D., S.B.F.), University Medicine Greifswald, Germany., Linneberg A; Department of Clinical Medicine (A.L.), Faculty of Health & Medicine Sciences, University of Copenhagen, Denmark.; Center for Clinical Research & Prevention, Bispebjerg & Frederiksberg Hospital, Copenhagen, Denmark (A.L.)., Hansen T; Novo Nordisk Foundation Center for Basic Metabolic Research (N.G., T.H.), Faculty of Health & Medicine Sciences, University of Copenhagen, Denmark., Arking DE; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (N.A.B., D.E.A.)., Kooperberg C; Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (J.H., C.K.)., Benjamin EJ; Boston University & NHLBI's Framingham Heart Study, Framingham, MA (H.L., J.K., E.J.B., K.L.L.).; Department of Medicine (E.J.B.), Boston University School of Medicine, Boston, MA.; Department of Epidemiology (E.J.B.), Boston University School of Public Health, Boston, MA., Lunetta KL; Boston University & NHLBI's Framingham Heart Study, Framingham, MA (H.L., J.K., E.J.B., K.L.L.).; Department of Biostatistics (K.L.L.), Boston University School of Public Health, Boston, MA., Ellinor PT; Cardiovascular Research Center (L.-C.W., A.W.H., P.L.H., P.T.E.), MGH, Boston.; Cardiac Arrhythmia Service (P.T.E, S.A.L.), MGH, Boston.; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA (L.-C.W., A.W.H., S.H.C., S.J.J., P.T.E., S.A.L.)., Lubitz SA; Cardiac Arrhythmia Service (P.T.E, S.A.L.), MGH, Boston.; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA (L.-C.W., A.W.H., S.H.C., S.J.J., P.T.E., S.A.L.).
Jazyk:	angličtina
Zdroj:	Circulation. Genomic and precision medicine [Circ Genom Precis Med] 2020 Oct; Vol. 13 (5), pp. 387-395. Date of Electronic Publication: 2020 Aug 21.
DOI:	10.1161/CIRCGEN.119.002874
Abstrakt:	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.
Databáze:	MEDLINE
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