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41.4 Mechanisms of atrial fibrillation: genetics
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Published:July 2018
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Abstract
While atrial fibrillation (AF) is common and has serious consequences, a lot is yet unknown about the causative factors underlying this arrhythmia. The role of genetics in the development of AF has become more evident in the past decade. Family history is now a firmly established risk factor and many common and rare sequence variants linked to AF have been identified. Genome-wide association studies have identified common sequence variants that associate with AF, including variants on chromosomes 4q25, 16q22, and 1q22. Nevertheless, it has become apparent that despite these findings, a substantial fraction of heritability of most complex traits remained unaccounted for. This raises the possibility that development of AF is determined by the combination of common and rare susceptibility variants. Whole genome sequencing is the most comprehensive method to analyse individual genetic variation. A paradigm shift from microarray-based genotyping studies to whole exome and whole genome sequencing is ongoing. Whole genome sequencing studies have shown mutations in myosin genes may be associated with AF, implying that variants encoding sarcomere genes may be involved in the development of this arrhythmia. While some of the sequence variants discovered suggest novel mechanisms in the pathophysiology of this complex arrhythmia, much work is still needed to fully understand the mechanisms linking many of these loci to AF. Likewise, the current clinical applicability of this information is still unclear. However, further developments in this field are expected to add to our understanding of this complex arrhythmia and hopefully lead to new therapeutic possibilities.
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