Key result
3D CMR mass univariate framework substantially boosts statistical power for cardiac genotype-phenotype associations.
Why the study?
Left ventricular hypertrophy is a strong predictor of cardiovascular outcomes, but its genetic regulation remains largely unexplained and conventional phenotyping is limited.
Answers are grounded in this paper and cite their sources.
A novel 3D cardiovascular imaging-genetics framework improves statistical power for mapping genotype-phenotype associations in the heart.
Motivation: Left ventricular (LV) hypertrophy is a strong predictor of cardiovascular outcomes, but its genetic regulation remains largely unexplained. Conventional phenotyping relies on manual calculation of LV mass and wall thickness, but advanced cardiac image analysis presents an opportunity for high-throughput mapping of genotype-phenotype associations in three dimensions (3D). Results: High-resolution cardiac magnetic resonance images were automatically segmented in 1124 healthy volunteers to create a 3D shape model of the heart. Mass univariate regression was used to plot a 3D effect-size map for the association between wall thickness and a set of predictors at each vertex in the mesh. The vertices where a significant effect exists were determined by applying threshold-free cluster enhancement to boost areas of signal with spatial contiguity. Experiments on simulated phenotypic signals and SNP replication show that this approach offers a substantial gain in statistical power for cardiac genotype-phenotype associations while providing good control of the false discovery rate. This framework models the effects of genetic variation throughout the heart and can be automatically applied to large population cohorts. Availability and implementation: The proposed approach has been coded in an R package freely available at https://doi.org/10.5281/zenodo.834610 together with the clinical data used in this work. Contact: declan.oregan@imperial.ac.uk. Supplementary information: Supplementary data are available at Bioinformatics online.
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Biffi et al. (2017) studied Healthy volunteers (n=1,124). Mass univariate regression framework for 3D cardiovascular imaging-genetics was evaluated on Statistical power for cardiac genotype-phenotype associations and control of false discovery rate. A mass univariate framework using 3D cardiac magnetic resonance imaging offered a substantial gain in statistical power for cardiac genotype-phenotype associations while controlling the false discovery rate.
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