Three-dimensional cardiovascular imaging-genetics: a mass univariate framework

Biffi, C., de Marvao, A., Attard, M. I., Dawes, T. J. W., Whiffin, N., Bai, W., Shi, W., Francis, C., Meyer, H., Buchan, R., Cook, S. A., Rueckert, D., O'Regan, D. P. (January 2018) Three-dimensional cardiovascular imaging-genetics: a mass univariate framework. Bioinformatics, 34 (1). pp. 97-103. ISSN 1367-4803

URL: ttps://www.ncbi.nlm.nih.gov/pubmed/28968671
DOI: 10.1093/bioinformatics/btx552

Abstract

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.

Item Type: Paper
Subjects: diseases & disorders > cardiovascular diseases
bioinformatics > genomics and proteomics > computers > computer software
CSHL Authors:
Communities: CSHL labs > Meyer Lab
Depositing User: Matthew Dunn
Date: 1 January 2018
Date Deposited: 25 Mar 2019 14:34
Last Modified: 25 Mar 2019 14:34
PMCID: PMC5870605
Related URLs:
URI: http://repository.cshl.edu/id/eprint/37741

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