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Meta-Analysis of Genome-Wide Association Studies Reveals Genetic Mechanisms of Supraventricular Arrhythmias.
Weng, Lu-Chen; Khurshid, Shaan; Hall, Amelia Weber; Nauffal, Victor; Morrill, Valerie N; Sun, Yan V; Rämö, Joel T; Beer, Dominik; Lee, Simon; Nadkarni, Girish; Johnson, Renee; Andreasen, Laura; Clayton, Anne; Pullinger, Clive R; Yoneda, Zachary T; Friedman, Daniel J; Hyman, Matthew C; Judy, Renae L; Skanes, Allan C; Orland, Kate M; Jordà, Paloma; Treu, Timothy M; Oetjens, Matthew T; Subbiah, Rajesh; Hartmann, Jacob P; May, Heidi T; Kane, John P; Issa, Tariq Z; Nafissi, Navid A; Leong-Sit, Peter; Dubé, Marie-Pierre; Roselli, Carolina; Choi, Seung Hoan; Tardif, Jean-Claude; Khan, Habib R; Knight, Stacey; Svendsen, Jesper H; Walker, Bruce; Karlsson Linnér, Richard; Gaziano, J Michael; Tadros, Rafik; Fatkin, Diane; Rader, Daniel J; Shah, Svati H; Roden, Dan M; Marcus, Gregory M; Loos, Ruth J F; Damrauer, Scott M; Haggerty, Christopher M; Cho, Kelly.
Afiliación
  • Weng LC; Cardiovascular Research Center (L.-C.W.), The Broad Institute of MIT and Harvard, Cambridge.
  • Khurshid S; 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; VA Boston Healthcare System (L.-C.W., V.N., T.M.T., J.M.G., K.C.), Brigham and Women's Hospital, Boston, MA.
  • Nauffal V; Demoulas Center for Cardiac Arrhythmias (S. Khurshid, P.T.E., S.A.L.), The Broad Institute of MIT and Harvard, Cambridge.
  • 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; Gene Regulation Observatory (A.W.H.), The Broad Institute of MIT and Harvard, Cambridge.
  • 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.
  • Beer D; VA Boston Healthcare System (L.-C.W., V.N., T.M.T., J.M.G., K.C.), Brigham and Women's Hospital, Boston, MA.
  • Lee S; 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.
  • Nadkarni G; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA (Y.V.S.).
  • Johnson R; VA Atlanta Healthcare System, Decatur, GA (Y.V.S., P.W.F.W.).
  • Andreasen L; 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.
  • Clayton A; Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Finland (J.T.R., A.P.).
  • Pullinger CR; Heart Institute (D.B., C.M.H.), Geisinger, Danville, PA.
  • Yoneda ZT; Icahn School of Medicine at Mount Sinai, New York, NY (S.L., G.N.).
  • Friedman DJ; Icahn School of Medicine at Mount Sinai, New York, NY (S.L., G.N.).
  • Hyman MC; Victor Chang Cardiac Research Institute (R.J., R.S., D.F.), Darlinghurst, NSW.
  • Judy RL; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, NSW, Australia (R.J., R.S., B.W., D.F.).
  • Skanes AC; Department of Cardiology, Laboratory for Molecular Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark (L.A., J.P.H., J.H.S., M.S.O.).
  • Orland KM; Department of Biomedical Sciences (L.A., M.S.O.), University of Copenhagen, Denmark.
  • Jordà P; Intermountain Heart Institute, Intermountain Medical Center, Murray, UT (A.C., H.T.M., S. Knight, M.J.C.).
  • Treu TM; Cardiovascular Research Institute and Department of Physiological Nursing (C.R.P.), University of California, San Francisco.
  • Oetjens MT; Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN (Z.T.Y., M.B.S.).
  • Subbiah R; Division of Cardiology, Department of Medicine (D.J.F., N.A.N., S.H.S.), Duke University School of Medicine, Durham, NC.
  • Hartmann JP; Division of Cardiac Electrophysiology, Hospital of the University of Pennsylvania, Philadelphia (M.C.H.).
  • May HT; Department of Surgery (R.L.J.), University of Pennsylvania, Philadelphia.
  • Kane JP; 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.).
  • Issa TZ; Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin-Madison, WI (K.M.O., L.L.E.).
  • Nafissi NA; Montreal Heart Institute Research Center and Faculty of Medicine, Université de Montréal, QC, Canada (P.J., M.-P.D., J.-C.T., R.T.).
  • Leong-Sit P; VA Boston Healthcare System (L.-C.W., V.N., T.M.T., J.M.G., K.C.), Brigham and Women's Hospital, Boston, MA.
  • Dubé MP; Autism and Developmental Medicine Institute, Geisinger, Lewisburg, PA (M.T.O., R.K.L.).
  • Roselli C; Victor Chang Cardiac Research Institute (R.J., R.S., D.F.), Darlinghurst, NSW.
  • Choi SH; St Vincent's Hospital (R.S., B.W., D.F.), Darlinghurst, NSW.
  • Tardif JC; Department of Cardiology, Laboratory for Molecular Cardiology, Copenhagen University Hospital, Rigshospitalet, Denmark (L.A., J.P.H., J.H.S., M.S.O.).
  • Khan HR; Intermountain Heart Institute, Intermountain Medical Center, Murray, UT (A.C., H.T.M., S. Knight, M.J.C.).
  • Knight S; Cardiovascular Research Institute (J.P.K.), University of California, San Francisco.
  • Svendsen JH; Department of Medicine, Department of Biochemistry and Biophysics (J.P.K.), University of California, San Francisco.
  • Walker B; Feinberg School of Medicine, Northwestern University, Chicago, IL (T.Z.I.).
  • Karlsson Linnér R; Division of Cardiology, Department of Medicine (D.J.F., N.A.N., S.H.S.), Duke University School of Medicine, Durham, NC.
  • Gaziano JM; 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.).
  • 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; Beaulieu-Saucier Pharmacogenomics Center, Montreal, QC, Canada (M.-P.D.).
  • Rader DJ; 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.
  • Shah SH; Department of Cardiology, University of Groningen, University Medical Center Groningen, the Netherlands (C.R.).
  • Roden DM; 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.
  • Loos RJF; Montreal Heart Institute Research Center and Faculty of Medicine, Université de Montréal, QC, Canada (P.J., M.-P.D., J.-C.T., R.T.).
  • Damrauer SM; 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.).
  • Haggerty CM; Intermountain Heart Institute, Intermountain Medical Center, Murray, UT (A.C., H.T.M., S. Knight, M.J.C.).
  • Cho K; Department of Medicine, University of Utah, Salt Lake City (S. Knight).
Circ Genom Precis Med ; 17(3): e004320, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38804128
ABSTRACT

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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Taquicardia Supraventricular / Estudio de Asociación del Genoma Completo Límite: Humans Idioma: En Revista: Circ Genom Precis Med Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Taquicardia Supraventricular / Estudio de Asociación del Genoma Completo Límite: Humans Idioma: En Revista: Circ Genom Precis Med Año: 2024 Tipo del documento: Article