Genetic and environmental determinants of diastolic heart function

Thanaj, Marjola, Mielke, Johanna, McGurk, Kathryn, Bai, Wenjia, Savioli, Nicoló, de Marvao, Antonio, Meyer, Hannah, Zeng, Lingyao, Sohler, Florian, Wilkins, Martin, Ware, James, Bender, Christian, Rueckert, Daniel, MacNamara, Aidan, Freitag, Daniel, O’Regan, Declan (2021) Genetic and environmental determinants of diastolic heart function. medRxiv. (Submitted)

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DOI: 10.1101/2021.06.07.21257302


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 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 ventricular stiffness and heart failure. Our results provide novel insights into the genetic and environmental factors influencing diastolic function that are relevant for identifying causal relationships and tractable targets in heart failure.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions
organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:
Communities: CSHL labs > Meyer Lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 2021
Date Deposited: 20 Dec 2023 19:52
Last Modified: 20 Dec 2023 19:52
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