Genetic and environmental determinants of diastolic heart function

Thanaj, Marjola, Mielke, Johanna, McGurk, Kathryn A, Bai, Wenjia, Savioli, Nicolò, de Marvao, Antonio, Meyer, Hannah V, Zeng, Lingyao, Sohler, Florian, Lumbers, R Thomas, Wilkins, Martin R, Ware, James S, Bender, Christian, Rueckert, Daniel, MacNamara, Aidan, Freitag, Daniel F, O'Regan, Declan P (April 2022) Genetic and environmental determinants of diastolic heart function. Nat Cardiovasc Res, 1 (4). pp. 361-371. ISSN 2731-0590

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DOI: 10.1038/s44161-022-00048-2


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.

Item Type: Paper
Subjects: diseases & disorders > cardiovascular diseases
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
CSHL Authors:
Communities: CSHL labs > Meyer Lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 13 April 2022
Date Deposited: 02 May 2022 14:26
Last Modified: 02 May 2022 14:26
PMCID: PMC7612636

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