Nature genetics · 2025

The impact of common and rare genetic variants on bradyarrhythmia development.

СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди

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Weng Lu-Chen, Rämö Joel T, Jurgens Sean J, Khurshid Shaan, Chaffin Mark, Hall Amelia Weber, Morrill Valerie N, Wang Xin, Nauffal Victor, Sun Yan V, Beer Dominik, Lee Simon, Nadkarni Girish N, Duong ThuyVy, Wang Biqi, Czuba Tomasz, Austin Thomas R, Yoneda Zachary T, Friedman Daniel J, Clayton Anne, Hyman Matthew C, Judy Renae L, Skanes Allan C, Orland Kate M, Treu Timothy M, Oetjens Matthew T, Alonso Alvaro, Soliman Elsayed Z, Lin Honghuang, Lunetta Kathryn L, van der Pals Jesper, Issa Tariq Z, Nafissi Navid A, May Heidi T, Leong-Sit Peter, Roselli Carolina, Choi Seung Hoan, FinnGen, Million Veteran Program, Regeneron Genetics Center, Khan Habib R, Knight Stacey, Karlsson Linnér Richard, Bezzina Connie R, Ripatti Samuli, Heckbert Susan R, Gaziano J Michael, Loos Ruth J F, Psaty Bruce M, Smith J Gustav, Benjamin Emelia J, Arking Dan E, Rader Daniel J, Shah Svati H, Roden Dan M, Damrauer Scott M, Eckhardt Lee L, Roberts Jason D, Cutler Michael J, Shoemaker M Benjamin, Haggerty Christopher M, Cho Kelly, Palotie Aarno, Wilson Peter W F, Ellinor Patrick T, Lubitz Steven A

Аннотация

To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively. Four well-known loci (SCN5A/SCN10A, CCDC141, TBX20 and CAMK2D) were shared for SND and DCD, while others were more specific for SND or DCD. SND and DCD showed a moderate genetic correlation (rg = 0.63). Cardiomyocyte-expressed genes were enriched for contributions to DCD heritability. Rare-variant analyses implicated LMNA for all bradyarrhythmia phenotypes, SMAD6 and SCN5A for DCD and TTN, MYBPC3 and SCN5A for PM. These results show that variation in multiple genetic pathways (for example, ion channel function, cardiac developmental programs, sarcomeric structure and cellular homeostasis) appear critical to the development of bradyarrhythmias.

Предметные рубрики MeSH

Humans Bradycardia Genome-Wide Association Study Genetic Predisposition to Disease Genetic Variation Polymorphism, Single Nucleotide NAV1.5 Voltage-Gated Sodium Channel Sick Sinus Syndrome Female Male Phenotype Pacemaker, Artificial Cardiac Conduction System Disease

The impact of common and rare genetic variants on bradyarrhythmia development.

Ошибки и ограничения

Аннотация

Предметные рубрики MeSH