Atrial fibrillation (AF), a common form of irregular heartbeat that increases the risk of stroke and heart failure, is often inherited; however, few genetic loci for AF have been identified. Müller, Melville et al. now identify an AF-associated variant in the coding sequence of GREMLIN2 (GREM2), an inhibitor of bone morphogenetic protein (BMP). Cardiac laterality and atrial differentiation were defective in grem2-depleted zebrafish embryos, the researchers report, and functional modelling of the GREM2 human mutation showed that GREM2 overactivity slowed cardiac rates and induced the expression of previously identified AF candidate genes. GREM2 overexpression also disturbed the propagation and velocity of contraction waves in atrial cardiomyocytes in zebrafish hearts. These results implicate regulators of BMP signalling in the pathogenesis of AF and identify new therapeutic targets. Page 332
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