Atrial fibrillation associations from whole-genome sequence data now available in the CVDKP

We are pleased to present in the Cardiovascular Disease Knowledge Portal the results of a new study, published today in the Journal of the American Medical Association, that used deep-coverage whole-genome sequencing to uncover genetic variants contributing to early-onset atrial fibrillation. As part of the NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium and the DiscovEHR study, first author Seung Hoan Choi and colleagues analyzed genetic associations with early-onset atrial fibrillation (AF) in 2,781 cases and 4,959 controls.

The study found multiple associations of common variants with AF, many of which supported previous reports. One particularly interesting association was found for a variant in an intron of the NAV2 gene. Since NAV2 is involved in nervous system development, this association may suggest a link between AF and development of the autonomic nervous system.

The researchers also took advantage of the whole-genome sequence data to assess the contribution of rare loss-of-function (LOF) variants to early-onset AF. They analyzed the genes at 26 AF-associated loci, and found that rare LOF variants in the TTN gene were associated with early-onset AF, and furthermore were enriched in patients with earlier ages of AF onset. The association and enrichment could be replicated in exome sequencing datasets.

The Titin protein encoded by TTN is known to have a critical role in assembly and function of striated muscle tissue, and TTN mutations have been linked to cardiomyopathies. The discovery in this study of the association between LOF variants and early-onset AF points the way to future investigations of the involvement of Titin with AF that will lead to a better understanding of how AF develops.  For a more detailed summary of the work, see this coverage from the Broad Institute.

Summary statistics from this study are both integrated into the CVDKP and available for download from the Data page. The dataset is named Early-onset AF TOPMed WGS in the CVDKP and the results may be viewed:

  • on Gene pages on the Common Variants and High-impact Variants tabs  
  • on Variant pages in the Associations across all datasets graphic and table  
  • via the Variant Finder search tool
  • in a Manhattan plot accessible from the View full genetic association results menu on the CVDKP home page (select the atrial fibrillation phenotype and then select the Early-onset AF TOPMed WGS dataset to view the plot)
Please check out the new dataset and contact us with any comments, suggestions, or questions!


Popular posts from this blog

New polygenic risk score data and new features in the CVDKP

Large new atrial fibrillation dataset now in the CVDKP

Announcing the Cardiovascular Disease Knowledge Portal