Whole Exome Sequencing in Atrial Fibrillation


Atrial fibrillation is a common and morbid cardiac arrhythmia. Atrial fibrillation is heritable, and numerous genome-wide susceptibility loci have been identified, predominantly in non-coding regions. Over 35 genes also have been implicated in atrial fibrillation pathogenesis mostly through prior smaller scale candidate gene association studies, which generally did not have robust replication to support the associations. Therefore, the role of coding variation in the biology of atrial fibrillation is unclear. We examined whole exome sequencing data from 1,734 individuals with and 9,423 without atrial fibrillation, and did not observe any significant associations between coding variation and the arrhythmia. Furthermore, we did not observe any enrichment for association in previously implicated atrial fibrillation genes. In aggregate, our findings suggest that large effect coding variation is unlikely to be a predominant mechanism of common forms of atrial fibrillation encountered in the community.


Vyšlo v časopise: Whole Exome Sequencing in Atrial Fibrillation. PLoS Genet 12(9): e32767. doi:10.1371/journal.pgen.1006284
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1006284

Souhrn

Atrial fibrillation is a common and morbid cardiac arrhythmia. Atrial fibrillation is heritable, and numerous genome-wide susceptibility loci have been identified, predominantly in non-coding regions. Over 35 genes also have been implicated in atrial fibrillation pathogenesis mostly through prior smaller scale candidate gene association studies, which generally did not have robust replication to support the associations. Therefore, the role of coding variation in the biology of atrial fibrillation is unclear. We examined whole exome sequencing data from 1,734 individuals with and 9,423 without atrial fibrillation, and did not observe any significant associations between coding variation and the arrhythmia. Furthermore, we did not observe any enrichment for association in previously implicated atrial fibrillation genes. In aggregate, our findings suggest that large effect coding variation is unlikely to be a predominant mechanism of common forms of atrial fibrillation encountered in the community.


Zdroje

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Genetika Reprodukčná medicína
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