Genetics, transcriptomics, metagenomics, and metabolomics in the pathogenesis and prediction of atrial fibrillation
: Linna-Kuosmanen, Suvi; Vuori, Matti; Kiviniemi, Tuomas; Palmu, Joonatan; Niiranen, Teemu
Publisher: Oxford University Press
: 2024
: European Heart Journal Supplements
: European heart journal supplements : journal of the European Society of Cardiology
: Eur Heart J Suppl
: 26
: Suppl 4
: iv33
: iv40
: 1520-765X
: 1554-2815
DOI: https://doi.org/10.1093/eurheartjsupp/suae072
: https://academic.oup.com/eurheartjsupp/article/26/Supplement_4/iv33/7725447
: https://research.utu.fi/converis/portal/detail/Publication/457436814
The primary cellular substrates of atrial fibrillation (AF) and the mechanisms underlying AF onset remain poorly characterized and therefore, its risk assessment lacks precision. While the use of omics may enable discovery of novel AF risk factors and narrow down the cellular pathways involved in AF pathogenesis, the work is far from complete. Large-scale genome-wide association studies and transcriptomic analyses that allow an unbiased, non-candidate-gene-based delineation of molecular changes associated with AF in humans have identified at least 150 genetic loci associated with AF. However, only few of these loci have been thoroughly mechanistically dissected, indicating that much remains to be discovered for targeted diagnostics and therapeutics. Metabolomics and metagenomics, on the other hand, add to the understanding of AF downstream of the primary substrate and integrate the signalling of environmental and host factors, respectively. These two rapidly developing fields have already provided several correlates of prevalent and incident AF that require additional validation in external cohorts and experimental studies. In this review, we take a look at the recent developments in genetics, transcriptomics, metagenomics, and metabolomics and how they may aid in improving the discovery of AF risk factors and shed light into the molecular mechanisms leading to AF onset.
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This work was supported by: The Research Council of Finland grants 342074 to S.L.-K. and 321351 and 354447 to T.N., Aarne Koskelo Foundation to S.L.-K., EU/Horizon-EIC-Pathfinder-MIRACLE to T.K., EU/Horizon 2020/Business Finland-Moore4Medidal to T.K., Finnish Foundation for Cardiovascular Research to S.L.-K., T.K., and T.N., Sigrid Jusélius Foundation to T.N., the Finnish Medical Foundation, and State Research Funds to T.K.
