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Relevance of Multi-Omics Studies in Cardiovascular Diseases.

ABSTRACT: Cardiovascular diseases are the leading cause of death around the world. Despite the larger number of genes and loci identified, the precise mechanisms by which these genes influence risk of cardiovascular disease is not well understood. Recent advances in the development and optimization of high-throughput technologies for the generation of "omics data" have provided a deeper understanding of the processes and dynamic interactions involved in human diseases. However, the integrative analysis of "omics" data is not straightforward and represents several logistic and computational challenges. In spite of these difficulties, several studies have successfully applied integrative genomics approaches for the investigation of novel mechanisms and plasma biomarkers involved in cardiovascular diseases. In this review, we summarized recent studies aimed to understand the molecular framework of these diseases using multi-omics data from mice and humans. We discuss examples of omics studies for cardiovascular diseases focused on the integration of genomics, epigenomics, transcriptomics, and proteomics. This review also describes current gaps in the study of complex diseases using systems genetics approaches as well as potential limitations and future directions of this emerging field.

SUBMITTER: Leon-Mimila P

PROVIDER: S-EPMC6656333 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Relevance of Multi-Omics Studies in Cardiovascular Diseases.

Leon-Mimila Paola P Wang Jessica J Huertas-Vazquez Adriana A

Frontiers in cardiovascular medicine 20190717

Cardiovascular diseases are the leading cause of death around the world. Despite the larger number of genes and loci identified, the precise mechanisms by which these genes influence risk of cardiovascular disease is not well understood. Recent advances in the development and optimization of high-throughput technologies for the generation of "omics data" have provided a deeper understanding of the processes and dynamic interactions involved in human diseases. However, the integrative analysis of ...[more]

PMID: 31380393

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Project description:BackgroundCardiovascular diseases (CVDs) are major causes of mortality and morbidity worldwide; yet the understanding of their molecular basis is incomplete. Multi-omics studies have significant potential to uncover these mechanisms, but such studies are challenged by genetic and environmental confounding-a problem that can be effectively reduced by investigating intrapair differences in twins. Here, we linked data on all diagnoses of the circulatory system from the nationwide Danish Patient Registry (spanning 1977-2022) to a study population of 835 twins holding genome-wide DNA methylation and gene expression data. CVD diagnoses were divided into prevalent or incident cases (i.e., occurring before or after blood sample collection (2007-2011)). The diagnoses were classified into four groups: cerebrovascular diseases, coronary artery disease (CAD), arterial and other cardiovascular diseases (AOCDs), and diseases of the veins and lymphatic system. Statistical analyses were performed by linear (prevalent cases) or cox (incident cases) regression analyses at both the individual-level and twin pair-level. Significant genes (p < 0.05) in both types of biological data and at both levels were inspected by bioinformatic analyses, including gene set enrichment analysis and interaction network analysis.ResultsIn general, more genes were found for prevalent than for incident cases, and bioinformatic analyses primarily found pathways of the immune system, signal transduction and diseases for prevalent cases, and pathways of cell-cell communication, metabolisms of proteins and RNA, gene expression, and chromatin organization groups for incident cases. This potentially reflects biology related to response to CVD (prevalent cases) and mechanisms related to regulation and development of disease (incident cases). Of specific genes, Myosin 1E was found to be central for CAD, and DEAD-Box Helicase 5 for AOCD. These genes were observed in both the prevalent and the incident analyses, potentially reflecting that their DNA methylation and gene transcription levels change both because of disease (prevalent cases) and prior disease (incident cases).ConclusionWe present novel biomarkers for CVD by performing multi-omics analysis in twins, hereby lowering the confounding due to shared genetics and early life environment-a study design that is surprisingly rare in the field of CVD, and where additional studies are highly needed.

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Relevance of Multi-Omics Studies in Cardiovascular Diseases.

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Relevance of Multi-Omics Studies in Cardiovascular Diseases.

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