Since the 1990s, genetic testing in cardiology has been recommended primarily for people with symptoms of an inherited cardiovascular disease or for those at high risk due to the presence of a pathogenic genetic variant previously identified in their family. In 2020, the American Heart Association (AHA) reinforced this strategy by recommending genetic testing for patients diagnosed with various forms of cardiomyopathies, heart rhythm disorders, inherited vascular diseases, and lipid disorders such as familial hypercholesterolemia.
Currently, specialists have access to a wide range of genetic analysis tools, ranging from the sequencing of a single gene or specific panels associated with a particular disease to whole-exome sequencing (WES) and whole-genome sequencing (WGS). Although the latter is used primarily in research, its clinical application is increasing thanks to its ability to identify new associations between genes and diseases.
Genomic studies have shown that many cardiovascular diseases are not caused by a single genetic mutation, but rather by a combination of numerous common variants with small effects, known as single-nucleotide polymorphisms (SNPs). Collectively, these variants can significantly increase the risk of developing cardiovascular disease.
Genomic studies have shown that many cardiovascular diseases are not caused by a single genetic mutation.
Based on this information, it is possible to calculate polygenic risk scores—tools that estimate a person’s genetic predisposition even before the first symptoms appear. The ability to identify individuals at higher risk and implement early preventive strategies could drive the gradual incorporation of WES and WGS testing into routine clinical practice.
However, cardiogenomics remains a constantly evolving field. A significant proportion of the identified genetic variants are currently classified as variants of uncertain clinical significance (VUS), as there is insufficient evidence to determine whether or not they contribute to the development of the disease. Therefore, further studies are needed to better understand how these variants interact with other genes and environmental factors in order to establish their true clinical relevance.
Furthermore, the integration of genetic information with other omics disciplines, such as proteomics and metabolomics, is providing a more comprehensive view of the biological mechanisms involved in cardiovascular diseases. This multidimensional approach will help improve our understanding of their pathophysiology and facilitate the development of more precise diagnostic and therapeutic strategies.
Clinical Applications of Cardiovascular Genetics
As our understanding of how genetic variations influence the development of diseases advances, new opportunities for precision medicine are emerging. This knowledge allows us to evaluate the efficacy and safety of existing treatments in specific patient groups, as well as to drive the development of new therapies targeting specific genetic alterations.
One example of this is long QT syndrome, an inherited heart disorder associated with an increased risk of arrhythmias. It is estimated that about 75% of cases are caused by pathogenic variants in genes that encode ion channel subunits, such as KCNQ1, KCNH2, and SCN5A. Identifying alterations in these genes not only helps confirm the diagnosis but also provides valuable information for selecting the most appropriate treatment and follow-up strategies for each patient.
Mutations in the genes that encode the subunits of ion channels (KCNQ1, KCNH2, SCN5A) account for 75% of cases of long QT syndrome.
However, the incorporation of genetic advances into clinical practice is not always immediate. A considerable amount of time typically elapses between the discovery of a genetic variant associated with a cardiovascular disease and its routine application in clinical care; during this period, it is necessary to generate sufficient clinical evidence to support its diagnostic and therapeutic utility.
A good example is hereditary cardiac amyloidosis, a disease caused by the deposition of amyloid proteins in heart tissue, which progressively impairs the heart’s ability to pump blood. Although effective treatments for this condition are currently available and the key role of pathogenic variants in the TTR gene in its development is well understood, the lack of systematic implementation of genetic testing can delay diagnosis and limit some patients’ access to these therapies.
Similar situations are observed in other hereditary cardiovascular diseases. For example, analysis of the LMNA gene can provide relevant information in patients with dilated cardiomyopathy, while sequencing of genes such as LDLR, APOB, and PCSK9 is key to confirming the diagnosis of familial hypercholesterolemia and identifying individuals at significantly elevated risk for cardiovascular disease. However, despite their proven clinical utility, these genetic tests remain underutilized in many healthcare settings.
The gradual integration of genetics into clinical practice will improve early diagnosis, optimize treatment selection, and promote more personalized care for patients with hereditary cardiovascular diseases.
Our portfolio of targeted exome sequencing
At Dreamgenics, we offer 19 targeted exome tests across eight different clinical areas, in addition to our DG Cardiopathy targeted exome test, which covers 475 genes associated or potentially associated with the development of hereditary cardiovascular diseases, including cardiomyopathies, channelopathies, and aortopathies, as well as pulmonary hypertension and hypercholesterolemia. Recommended for complex cases without a definitive clinical diagnosis.
Cardiology · Clinical Areas
Genetic testing for hereditary cardiovascular diseases. Analysis of SNVs, Indels, and CNVs.
Conclusion
Understanding how the information contained in our DNA is regulated and expressed is essential for the development and implementation of personalized medicine in clinical practice. Identifying genetic variants with potential pathogenic relevance will improve the prevention, diagnosis, and treatment of numerous diseases, including cardiovascular diseases.
Although the application of genomics in cardiology is relatively recent compared to other medical fields, advances in this area are transforming the way these conditions are treated. As is already the case in disciplines such as oncology, understanding the genetic factors involved in the disease will make it possible to identify at an early stage those at highest risk, optimize preventive strategies, and facilitate earlier and more precise interventions.
All of this will help improve survival rates, reduce complications associated with cardiovascular disease, and improve patients' quality of life.
BIBLIOGRAPHY
- Kalia SS, et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med. 2017 Feb;19(2):249-255.
- Ahn J, et al. Effectiveness of beta-blockers depending on the genotype of congenital long-QT syndrome: A meta-analysis. PLoS One. 2017 Oct 23;12(10):e0185680.
- Park J, et al. A genome-first approach to aggregating rare genetic variants in LMNA for association with electronic health record phenotypes. Genet Med. 2020 Jan;22(1):102-111.
- Sturm AC, et al. Convened by the Familial Hypercholesterolemia Foundation. Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel. J Am Coll Cardiol. 2018 Aug 7;72(6):662-680.
- Damrauer SM, et al. Association of the V122I Hereditary Transthyretin Amyloidosis Genetic Variant With Heart Failure Among Individuals of African or Hispanic/Latino Ancestry. JAMA. 2019 Dec 10;322(22):2191-2202.
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