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Genetic analysis of complex cardiovascular traits


MRC London Institute of Medical Sciences (LMS)

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Dr D O'Regan , Dr J Ware No more applications being accepted Funded PhD Project (UK Students Only)

About the Project

The heart is a dynamic biomechanical phenotype, and discovering how genetic and environmental factors shape its structure and function is crucial for understanding the transition from health to disease. While conventional image-derived phenotypes have relied on simple measures of volumes and mass, we have shown the transformative potential for modelling complex traits that embed rich information on the dynamic physiology of the heart. For instance, our group has shown that deep-learning cardiac motion analysis can efficiently predict human survival and that fractal analysis reveals how structural complexity affects susceptibility to heart failure.

The aim of this project is to use high dimensional image-derived phenotypes collected in large biobanked-populations to identify the role of common and rare variants on the 3D geometry and motion of the heart in both health and disease. This project will exploit developments in dimensionality reduction and multi-trait analyses for genetic association, classification and prediction tasks. This work is at the intersection of multiple disciplines that include bioinformatics, data science and machine learning – and involves collaborating closely with clinicians in cardiology and radiology.

The project will involve training opportunities in translational medicine within a vibrant multidisciplinary biomedical research group. The ideal candidate will have an enthusiasm for combining cutting edge bioinformatics and data science to answer important questions in cardiovascular health.

To Apply please visit the LMS website - https://lms.mrc.ac.uk/study-here/phd-studentships/lms-3-5yr-studentships/


Funding Notes

This is a fully-funded 3.5 year studentship funded by the Medical Research Council.

The studentship covers all tuition fees with Imperial College London and stipend payments amounting to £21,000pa (paid in monthly instalments) directly to the student.

References

Meyer HV, Dawes TJW, Serrani M, Bai W, Tokarczuk P, Cai J, de Marvao A, Henry A, Lumbers RT, Gierten J, Thumberger T, Wittbrodt J, Ware JS, Rueckert D, Matthews PM, Prasad SK, Costantino ML, Cook SA, Birney E, O'Regan DP. Genetic and functional insights into the fractal structure of the heart. Nature. 2020 Aug;584(7822):589-594. doi: 10.1038/s41586-020-2635-8.

Bai W, Suzuki H, Huang J, Francis C, Wang S, Tarroni G, Guitton F, Aung N, Fung K, Petersen SE, Piechnik SK, Neubauer S, Evangelou E, Dehghan A, O'Regan DP, Wilkins MR, Guo Y, Matthews PM, Rueckert D. A population-based phenome-wide association study of cardiac and aortic structure and function. Nature Medicine. 2020 Aug 24. doi: 10.1038/s41591-020-1009-y.

Bello GA, Dawes TJW, Duan J, Biffi C, de Marvao A, Howard LSGE, Gibbs JSR, Wilkins MR, Cook SA, Rueckert D, O'Regan DP. Deep learning cardiac motion analysis for human survival prediction. Nature Mach Intell. 2019 Feb 11;1:95-104. doi: 10.1038/s42256-019-0019-2.


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