Cardiovascular Disease: From Genetics to Therapeutics

Dear Colleagues,

Human genetic studies, including common and rare variant association studies (GWAS, RVAS), phenotypic analyses in large biobanks (PheWAS) and other “omics” approaches (QTL, TWAS, and single cell studies), have identified thousands of genetic risk signals associated with cardiovascular disease and related phenotypes. These genetic data hold great potential for the discovery of novel disease mechanisms, drug targets, and therapeutic approaches. For example, most of the over 200 loci associated with coronary artery disease are not associated with circulating cholesterol or blood pressure (the two major risk factors for which we have effective therapeutics), suggesting the presence of additional disease mechanisms that are not currently being therapeutically targeted.

Discovering these new disease mechanisms, however, remains challenging because ~80% of likely causal disease variants are in non-coding regions of the genome. These variants likely modify the activities of regulatory elements, such as enhancers, that can each regulate multiple target genes, at great distances, and which can be highly cell type-specific. Moreover, determining the causal noncoding variant within a linkage disequilibrium block is difficult, relative to coding variants, because of limitations in our predictive tools. Even for coding variants, it remains non-trivial to understand their connections to disease. Accordingly, it has been extremely difficult to determine the target gene, relevant cell type, and mechanism for the vast majority of disease-associated loci.

Cardiovascular disease remains the leading cause of death worldwide, and there is a great unmet need for novel classes of therapeutics that might be discovered if we could unlock the ever-increasing wealth of information from human genetic studies. The challenge for the field, then, is to find ways to accelerate variant-to-function discovery for cardiovascular disease. This will require the development of better computational models to predict variant functions and higher throughput approaches to link variants to molecular and cellular phenotypes, together with an intensified effort to discover disease mechanisms for individual causal genes and pathways and to develop new therapeutics to target them.

This Special Issue cordially invites novel studies and review articles that address all aspects of genetics-to-therapeutics discovery for cardiovascular disease, including new genetic analyses/meta-analyses, predictive modeling, high-throughput variant-to-function approaches, single cell studies that identify pathogenic cell types or transcriptomic signatures, dissection of variant-to-disease mechanisms at individual loci, and efforts to develop new therapeutics targeting known or novel causal genes and pathways.

Dr. Gavin Schnitzler
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at mdpi.longhoe.net by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• cardiovascular disease
• genetics
• variant to function
• causal genes
• disease mechanism
• drug discovery