Weng, Lu-Chen and Khurshid, Shaan and Hall, Amelia Weber and Nauffal, Victor and Morrill, Valerie N. and Sun, Yan V. and Rämö, Joel T. and Beer, Dominik and Lee, Simon and Nadkarni, Girish and Johnson, Renee and Andreasen, Laura and Clayton, Anne and Pullinger, Clive R. and Yoneda, Zachary T. and Friedman, Daniel J. and Hyman, Matthew C. and Judy, Renae L. and Skanes, Allan C. and Orland, Kate M. and Jordà, Paloma and Treu, Timothy M. and Oetjens, Matthew T. and Subbiah, Rajesh and Hartmann, Jacob P. and May, Heidi T. and Kane, John P. and Issa, Tariq Z. and Nafissi, Navid A. and Leong-Sit, Peter and Dubé, Marie-Pierre and Roselli, Carolina and Choi, Seung Hoan and Tardif, Jean-Claude and Khan, Habib R. and Knight, Stacey and Svendsen, Jesper H. and Walker, Bruce and Karlsson Linnér, Richard and Gaziano, J. Michael and Tadros, Rafik and Fatkin, Diane and Rader, Daniel J. and Shah, Svati H. and Roden, Dan M. and Marcus, Gregory M. and Loos, Ruth J.F. and Damrauer, Scott M. and Haggerty, Christopher M. and Cho, Kelly and Palotie, Aarno and Olesen, Morten S. and Eckhardt, Lee L. and Roberts, Jason D. and Cutler, Michael J. and Shoemaker, M. Benjamin and Wilson, Peter W.F. and Ellinor, Patrick T. and Lubitz, Steven A. (2024) Meta-Analysis of Genome-Wide Association Studies Reveals Genetic Mechanisms of Supraventricular Arrhythmias. Circulation: Genomic and Precision Medicine, 17 (3). ISSN 2574-8300
Full text not available from this repository.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.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 25 Dec 2024 23:10 |
| Last Modified: | 25 Dec 2024 23:10 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1575 |
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