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Integration of Transformative Platforms for the Discovery of Causative Genes in Cardiovascular Diseases

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Abstract

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Genome-wide association studies (GWAS) are powerful epidemiological tools to find genes and variants associated with cardiovascular diseases while follow-up biological studies allow to better understand the etiology and mechanisms of disease and assign causality. Improved methodologies and reduced costs have allowed wider use of bulk and single-cell RNA sequencing, human-induced pluripotent stem cells, organoids, metabolomics, epigenomics, and novel animal models in conjunction with GWAS. In this review, we feature recent advancements relevant to cardiovascular diseases arising from the integration of genetic findings with multiple enabling technologies within multidisciplinary teams to highlight the solidifying transformative potential of this approach. Well-designed workflows integrating different platforms are greatly improving and accelerating the unraveling and understanding of complex disease processes while promoting an effective way to find better drug targets, improve drug design and repurposing, and provide insight towards a more personalized clinical practice.

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Funding

This work was partially supported by the National Institutes of Health HL138139 (J.Z.), HL109946, HL147527, HL137214, and HL134569 (Y.E.C.), and the American Heart Association Predoctoral Fellowship 17PRE33400179 (L.H).

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  1. Department of Internal Medicine, University of Michigan Medical Center, 2800 Plymouth Rd, Ann Arbor, MI, 48109-2800, USA

    Haocheng Lu, Jifeng Zhang, Y. Eugene Chen & Minerva T. Garcia-Barrio

  2. Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA

    Jifeng Zhang & Y. Eugene Chen

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  1. Haocheng Lu
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This manuscript was drafted by H.L and M.T.G-B, edited by J.Z and Y.E.C, and finalized by M.T.G-B and Y.E.C.

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Lu, H., Zhang, J., Chen, Y.E. et al. Integration of Transformative Platforms for the Discovery of Causative Genes in Cardiovascular Diseases. Cardiovasc Drugs Ther 35, 637–654 (2021). https://doi.org/10.1007/s10557-021-07175-1

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