A genome-wide association study of 39,559 UK Biobank participants identified nine independent loci associated with diastolic function traits and demonstrated a causal relationship between genetically determined ventricular stiffness and incident heart failure.
Observational (n=39,559)
Yes
This large-scale genome-wide association study identified 9 novel genetic loci associated with CMR-derived diastolic function traits and established a causal link between genetically determined ventricular stiffness and incident heart failure.
Diastole is the sequence of physiological events that occur in the heart during ventricular filling and principally depends on myocardial relaxation and chamber stiffness. Abnormal diastolic function is related to many cardiovascular disease processes and is predictive of health outcomes, but its genetic architecture is largely unknown. Here, we use machine learning cardiac motion analysis to measure diastolic functional traits in 39,559 participants of the UK Biobank and perform a genome-wide association study. We identified 9 significant, independent loci near genes that are associated with maintaining sarcomeric function under biomechanical stress and genes implicated in the development of cardiomyopathy. Age, sex and diabetes were independent predictors of diastolic function and we found a causal relationship between genetically-determined ventricular stiffness and incident heart failure. Our results provide insights into the genetic and environmental factors influencing diastolic function that are relevant for identifying causal relationships and potential tractable targets.
Thanaj et al. (Wed,) conducted a observational in Diastolic heart function (n=39,559). Genetic variants (Genome-Wide Association Study) was evaluated on Genetic loci associated with diastolic function traits (radial and longitudinal peak early diastolic strain rate and maximum indexed left atrial volume). A genome-wide association study of 39,559 UK Biobank participants identified nine independent loci associated with diastolic function traits and demonstrated a causal relationship between genetically determined ventricular stiffness and incident heart failure.