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April 13, 2022Nature Cardiovascular ResearchOpen Access

Genetic and environmental determinants of diastolic heart function

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Why the study?

Abnormal diastolic function is related to cardiovascular disease processes and predicts health outcomes, but its genetic architecture is largely unknown.

Population

39,559 participants of the UK Biobank

Design

Genome-wide association study using machine learning cardiac motion analysis

Key result

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.

Authors

MTMarjola ThanajJMJohanna MielkeKMKathryn A. McGurk

Discussion

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Overview

Supports causal role of ventricular stiffness in HF risk; leaves open whether loci guide prevention or therapy.

Study Design

Type

Observational (n=39,559)

Multicenter

Yes

Structured PICO

P
Population
39,559 community-dwelling participants aged 40-69 years from the UK Biobank with both cardiac magnetic resonance (CMR) imaging and genotyping array data.
O
Outcome
Diastolic functional traits measured by CMR: radial and longitudinal peak early diastolic strain rate (PDSRrr and PDSRll) and maximum body surface area-indexed left atrial volume (LAVmaxi).surrogate

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.

Limitations

  • The UK Biobank is subject to selection bias and latent population stratification.
  • The population is predominantly European, requiring further work to explore diastolic traits in people of diverse ancestries.
  • Measures of early diastolic strain rate may not capture variation in active relaxation before ventricular filling.
  • The relationship between quantitative and dichotomous outcomes may be nonlinear.

Cite This Study

Thanaj et al. (2022) conducted an 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.

synapsesocial.com/papers/6a051f480012b80f37a1feefhttps://doi.org/10.1038/s44161-022-00048-2
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