دورية أكاديمية
أعرض في EDS

Meta-Analysis of Genome-Wide Association Studies Reveals Genetic Mechanisms of Supraventricular Arrhythmias.

التفاصيل البيبلوغرافية
العنوان: Meta-Analysis of Genome-Wide Association Studies Reveals Genetic Mechanisms of Supraventricular Arrhythmias.
المؤلفون: Weng LC; Cardiovascular Research Center (L.-C.W.), The Broad Institute of MIT and Harvard, Cambridge.; Massachusetts General Hospital, Boston. Cardiovascular Disease Initiative (L.-C.W., S. Khurshid, V.N., V.N.M., J.T.R., C.R., S.H.C., P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge.; VA Boston Healthcare System (L.-C.W., V.N., T.M.T., J.M.G., K.C.), Brigham and Women's Hospital, Boston, MA., Khurshid S; Demoulas Center for Cardiac Arrhythmias (S. Khurshid, P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge.; Massachusetts General Hospital, Boston. Cardiovascular Disease Initiative (L.-C.W., S. Khurshid, V.N., V.N.M., J.T.R., C.R., S.H.C., P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge., Hall AW; Gene Regulation Observatory (A.W.H.), The Broad Institute of MIT and Harvard, Cambridge., Nauffal V; Massachusetts General Hospital, Boston. Cardiovascular Disease Initiative (L.-C.W., S. Khurshid, V.N., V.N.M., J.T.R., C.R., S.H.C., P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge.; VA Boston Healthcare System (L.-C.W., V.N., T.M.T., J.M.G., K.C.), Brigham and Women's Hospital, Boston, MA., Morrill VN; Massachusetts General Hospital, Boston. Cardiovascular Disease Initiative (L.-C.W., S. Khurshid, V.N., V.N.M., J.T.R., C.R., S.H.C., P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge., Sun YV; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA (Y.V.S.).; VA Atlanta Healthcare System, Decatur, GA (Y.V.S., P.W.F.W.)., Rämö JT; Massachusetts General Hospital, Boston. Cardiovascular Disease Initiative (L.-C.W., S. Khurshid, V.N., V.N.M., J.T.R., C.R., S.H.C., P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge.; Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Finland (J.T.R., A.P.)., Beer D; Heart Institute (D.B., C.M.H.), Geisinger, Danville, PA., Lee S; Icahn School of Medicine at Mount Sinai, New York, NY (S.L., G.N.)., Nadkarni G; Icahn School of Medicine at Mount Sinai, New York, NY (S.L., G.N.)., Johnson R; Victor Chang Cardiac Research Institute (R.J., R.S., D.F.), Darlinghurst, NSW.; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, NSW, Australia (R.J., R.S., B.W., D.F.)., Andreasen L; Department of Cardiology, Laboratory for Molecular Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark (L.A., J.P.H., J.H.S., M.S.O.).; Department of Biomedical Sciences (L.A., M.S.O.), University of Copenhagen, Denmark., Clayton A; Intermountain Heart Institute, Intermountain Medical Center, Murray, UT (A.C., H.T.M., S. Knight, M.J.C.)., Pullinger CR; Cardiovascular Research Institute and Department of Physiological Nursing (C.R.P.), University of California, San Francisco., Yoneda ZT; Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (Z.T.Y., M.B.S.)., Friedman DJ; Division of Cardiology, Department of Medicine (D.J.F., N.A.N., S.H.S.), Duke University School of Medicine, Durham, NC., Hyman MC; Division of Cardiac Electrophysiology, Hospital of the University of Pennsylvania, Philadelphia (M.C.H.)., Judy RL; Department of Surgery (R.L.J.), University of Pennsylvania, Philadelphia., Skanes AC; Division of Cardiology, Department of Medicine, Section of Cardiac Electrophysiology, Western University, London, ON, Canada (A.C.S., P.L.-S., H.R.K., J.D.R.)., Orland KM; Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin-Madison, WI (K.M.O., L.L.E.)., Jordà P; Montreal Heart Institute Research Center and Faculty of Medicine, Université de Montréal, QC, Canada (P.J., M.-P.D., J.-C.T., R.T.)., Treu TM; VA Boston Healthcare System (L.-C.W., V.N., T.M.T., J.M.G., K.C.), Brigham and Women's Hospital, Boston, MA., Oetjens MT; Autism and Developmental Medicine Institute, Geisinger, Lewisburg, PA (M.T.O., R.K.L.)., Subbiah R; Victor Chang Cardiac Research Institute (R.J., R.S., D.F.), Darlinghurst, NSW.; St Vincent's Hospital (R.S., B.W., D.F.), Darlinghurst, NSW.; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, NSW, Australia (R.J., R.S., B.W., D.F.)., Hartmann JP; Department of Cardiology, Laboratory for Molecular Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark (L.A., J.P.H., J.H.S., M.S.O.)., May HT; Intermountain Heart Institute, Intermountain Medical Center, Murray, UT (A.C., H.T.M., S. Knight, M.J.C.)., Kane JP; Cardiovascular Research Institute (J.P.K.), University of California, San Francisco.; Department of Medicine, Department of Biochemistry and Biophysics (J.P.K.), University of California, San Francisco., Issa TZ; Feinberg School of Medicine, Northwestern University, Chicago, IL (T.Z.I.)., Nafissi NA; Division of Cardiology, Department of Medicine (D.J.F., N.A.N., S.H.S.), Duke University School of Medicine, Durham, NC., Leong-Sit P; Division of Cardiology, Department of Medicine, Section of Cardiac Electrophysiology, Western University, London, ON, Canada (A.C.S., P.L.-S., H.R.K., J.D.R.)., Dubé MP; Montreal Heart Institute Research Center and Faculty of Medicine, Université de Montréal, QC, Canada (P.J., M.-P.D., J.-C.T., R.T.).; Beaulieu-Saucier Pharmacogenomics Center, Montreal, QC, Canada (M.-P.D.)., Roselli C; Massachusetts General Hospital, Boston. Cardiovascular Disease Initiative (L.-C.W., S. Khurshid, V.N., V.N.M., J.T.R., C.R., S.H.C., P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge.; Department of Cardiology, University of Groningen, University Medical Center Groningen, the Netherlands (C.R.)., Choi SH; Massachusetts General Hospital, Boston. Cardiovascular Disease Initiative (L.-C.W., S. Khurshid, V.N., V.N.M., J.T.R., C.R., S.H.C., P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge., Tardif JC; Montreal Heart Institute Research Center and Faculty of Medicine, Université de Montréal, QC, Canada (P.J., M.-P.D., J.-C.T., R.T.)., Khan HR; Division of Cardiology, Department of Medicine, Section of Cardiac Electrophysiology, Western University, London, ON, Canada (A.C.S., P.L.-S., H.R.K., J.D.R.)., Knight S; Intermountain Heart Institute, Intermountain Medical Center, Murray, UT (A.C., H.T.M., S. Knight, M.J.C.).; Department of Medicine, University of Utah, Salt Lake City (S. Knight)., Svendsen JH; Department of Cardiology, Laboratory for Molecular Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark (L.A., J.P.H., J.H.S., M.S.O.).; Department of Clinical Medicine (J.H.S.), University of Copenhagen, Denmark., Walker B; St Vincent's Hospital (R.S., B.W., D.F.), Darlinghurst, NSW.; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, NSW, Australia (R.J., R.S., B.W., D.F.)., Karlsson Linnér R; Autism and Developmental Medicine Institute, Geisinger, Lewisburg, PA (M.T.O., R.K.L.).; Department of Economics, Leiden Law School, Leiden University, the Netherlands (R.K.L.)., Gaziano JM; VA Boston Healthcare System (L.-C.W., V.N., T.M.T., J.M.G., K.C.), Brigham and Women's Hospital, Boston, MA.; Harvard Medical School, Boston, MA (J.M.G.)., Tadros R; Montreal Heart Institute Research Center and Faculty of Medicine, Université de Montréal, QC, Canada (P.J., M.-P.D., J.-C.T., R.T.)., Fatkin D; Victor Chang Cardiac Research Institute (R.J., R.S., D.F.), Darlinghurst, NSW.; St Vincent's Hospital (R.S., B.W., D.F.), Darlinghurst, NSW.; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, NSW, Australia (R.J., R.S., B.W., D.F.)., Rader DJ; Division of Cardiovascular Medicine, Department of Medicine (D.J.R.), University of Pennsylvania, Philadelphia., Shah SH; Division of Cardiology, Department of Medicine (D.J.F., N.A.N., S.H.S.), Duke University School of Medicine, Durham, NC.; Duke Molecular Physiology Institute (S.H.S.), Duke University School of Medicine, Durham, NC., Roden DM; Vanderbilt University Medical Center, Nashville, TN (D.M.R.)., Marcus GM; Division of Cardiology (G.M.M.), University of California, San Francisco., Loos RJF; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY (R.J.F.L.)., Damrauer SM; Department of Surgery and Department of Genetics, Perelman School of Medicine (S.M.D.), University of Pennsylvania, Philadelphia.; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA (S.M.D.)., Haggerty CM; Heart Institute (D.B., C.M.H.), Geisinger, Danville, PA.; Department of Translational Data Science and Informatics (C.M.H.), Geisinger, Danville, PA., Cho K; VA Boston Healthcare System (L.-C.W., V.N., T.M.T., J.M.G., K.C.), Brigham and Women's Hospital, Boston, MA., Palotie A; Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology, Department of Psychiatry (A.P.), The Broad Institute of MIT and Harvard, Cambridge.; The Stanley Center for Psychiatric Research & Program in Medical & Population Genetics (A.P.), The Broad Institute of MIT and Harvard, Cambridge.; Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Finland (J.T.R., A.P.)., Olesen MS; Department of Cardiology, Laboratory for Molecular Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark (L.A., J.P.H., J.H.S., M.S.O.).; Department of Biomedical Sciences (L.A., M.S.O.), University of Copenhagen, Denmark., Eckhardt LL; Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin-Madison, WI (K.M.O., L.L.E.)., Roberts JD; Division of Cardiology, Department of Medicine, Section of Cardiac Electrophysiology, Western University, London, ON, Canada (A.C.S., P.L.-S., H.R.K., J.D.R.)., Cutler MJ; Intermountain Heart Institute, Intermountain Medical Center, Murray, UT (A.C., H.T.M., S. Knight, M.J.C.)., Shoemaker MB; Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (Z.T.Y., M.B.S.)., Wilson PWF; Department of Medicine, Emory University School of Medicine, Atlanta, GA (P.W.F.W.)., Ellinor PT; Demoulas Center for Cardiac Arrhythmias (S. Khurshid, P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge.; Massachusetts General Hospital, Boston. Cardiovascular Disease Initiative (L.-C.W., S. Khurshid, V.N., V.N.M., J.T.R., C.R., S.H.C., P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge.; VA Atlanta Healthcare System, Decatur, GA (Y.V.S., P.W.F.W.)., Lubitz SA; Demoulas Center for Cardiac Arrhythmias (S. Khurshid, P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge.; Massachusetts General Hospital, Boston. Cardiovascular Disease Initiative (L.-C.W., S. Khurshid, V.N., V.N.M., J.T.R., C.R., S.H.C., P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge.
مؤلفون مشاركون: FinnGen, Million Veteran Program, Regeneron Genetics Center
المصدر: Circulation. Genomic and precision medicine [Circ Genom Precis Med] 2024 Jun; Vol. 17 (3), pp. e004320. Date of Electronic Publication: 2024 May 28.
نوع المنشور: Journal Article; Meta-Analysis
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 101714113 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2574-8300 (Electronic) Linking ISSN: 25748300 NLM ISO Abbreviation: Circ Genom Precis Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Baltimore, MD] : Lippincott Williams & Wilkins, [2018]-
مواضيع طبية MeSH: Genome-Wide Association Study* , Tachycardia, Supraventricular*/genetics, Humans ; Genetic Predisposition to Disease ; Tachycardia, Atrioventricular Nodal Reentry/genetics ; Polymorphism, Single Nucleotide ; Connectin/genetics ; Transcriptome
مستخلص: Background: Substantial data support a heritable basis for supraventricular tachycardias, but the genetic determinants and molecular mechanisms of these arrhythmias are poorly understood. We sought to identify genetic loci associated with atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular accessory pathways or atrioventricular reciprocating tachycardia (AVAPs/AVRT).
Methods: We performed multiancestry meta-analyses of genome-wide association studies to identify genetic loci for AVNRT (4 studies) and AVAP/AVRT (7 studies). We assessed evidence supporting the potential causal effects of candidate genes by analyzing relations between associated variants and cardiac gene expression, performing transcriptome-wide analyses, and examining prior genome-wide association studies.
Results: Analyses comprised 2384 AVNRT cases and 106 489 referents, and 2811 AVAP/AVRT cases and 1,483 093 referents. We identified 2 significant loci for AVNRT, which implicate NKX2-5 and TTN as disease susceptibility genes. A transcriptome-wide association analysis supported an association between reduced predicted cardiac expression of NKX2-5 and AVNRT. We identified 3 significant loci for AVAP/AVRT, which implicate SCN5A , SCN10A , and TTN/CCDC141 . Variant associations at several loci have been previously reported for cardiac phenotypes, including atrial fibrillation, stroke, Brugada syndrome, and electrocardiographic intervals.
Conclusions: Our findings highlight gene regions associated with ion channel function (AVAP/AVRT), as well as cardiac development and the sarcomere (AVAP/AVRT and AVNRT) as important potential effectors of supraventricular tachycardia susceptibility.
Competing Interests: Disclosures Dr Lubitz is a full-time employee of Novartis as of July 2022. Previously, Dr Lubitz received research support from Bristol Myers Squibb/Pfizer, Bayer AG, Boehringer Ingelheim, Fitbit, IBM, Medtronic, and Premier, Inc, and consulted for Bristol Myers Squibb/Pfizer, Bayer AG, Blackstone Life Sciences, and Invitae. Dr Ellinor receives research support from Bayer AG, IBM, and Bristol Myers Squibb/Pfizer and has consulted for Novartis, MyoKardia, and Bayer AG. Dr Damrauer receives research support for RenalytixAI and has consulted for Calico Labs. Dr Svendsen is a member of Medtronic advisory boards and has received speaker honoraria and research grants from Medtronic outside this work. Dr Cutler has consulted for Janssen Scientific. Dr Roselli is supported by a grant from Bayer AG to the Broad Institute focused on the development of therapeutics for cardiovascular disease. The other authors report no conflicts.
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معلومات مُعتمدة: K23 HL169839 United States HL NHLBI NIH HHS; R01 HL139731 United States HL NHLBI NIH HHS; R01 HL157635 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: atrial fibrillation; genome-wide association study; heart rate; heart ventricles; tachycardia, supraventricular
المشرفين على المادة: 0 (Connectin)
تواريخ الأحداث: Date Created: 20240528 Date Completed: 20240618 Latest Revision: 20240624
رمز التحديث: 20240625
مُعرف محوري في PubMed: PMC11187659
DOI: 10.1161/CIRCGEN.123.004320
PMID: 38804128
قاعدة البيانات: MEDLINE
الوصف
تدمد:2574-8300
DOI:10.1161/CIRCGEN.123.004320