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

Cardiovasc Drugs Ther. 2021 Jun;35(3):637-654. doi: 10.1007/s10557-021-07175-1. Epub 2021 Apr 15.

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.

Keywords: Animal models; GWAS; Multi-omics; Organoids; RNAseq; iPSC.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / genetics*
  • Disease Models, Animal
  • Epigenomics / methods
  • Genome-Wide Association Study
  • Humans
  • Induced Pluripotent Stem Cells / metabolism
  • Metabolomics / methods
  • Organoids / metabolism
  • RNA, Small Cytoplasmic / genetics
  • Sequence Analysis, RNA / methods

Substances

  • RNA, Small Cytoplasmic