5 Genetic Loci Linked to Dilated Cardiomyopathy in US Veterans

The following article is a part of conference coverage from the American Heart Association Scientific Sessions 2021, being held virtually from November 13 to 15, 2021. The team at Cardiology Advisor will be reporting on the latest news and research conducted by leading experts in cardiology. Check back for more from the AHA Scientific Sessions 2021.

The largest genome-wide association study (GWAS) to date has identified 5 common genetic loci associated with dilated cardiomyopathy (DCM) in United States Veterans. The study findings were presented at the American Heart Association (AHA) Scientific Sessions 2021, held from November 13 to 15, 2021.

Using electronic health record-based phenotyping, investigators defined DCM in the VA Million Veteran Program (MVP), performing ancestry-specific GWAS among participants of African and European genetic ancestry. Researchers also performed a transethnic meta-analysis and pursued the replication of sentinel DCM single nucleotide polymorphisms (SNPs) in the UK Biobank. They further examined the association between sentinel DCM SNPs and subclinical cardiac magnetic resonance imaging measures of left ventricular (LV) function and structure, as well as with hypertrophic cardiomyopathy (HCM) in MVP.

MVP participants had a mean age of 61.5 years; 9.6% were women; and 5597 had DCM. Of those with DCM, 1811 were of African ancestry and 3786 were of European ancestry. The transethnic meta-analysis identified 8 genomic regions associated with DCM at genome-wide significance (P <5×10^-8), including 3 of 4 known associations near HSPB7, LSM3, and BAG3, as well as 5 novel genomic regions near SLC39A8, CDKN1A, CD36, NEDD4L, and MAP3K7CL.

In the UK Biobank, 3 of the novel regions were replicated (at CDKN1A, NEDD4L, and MAP3K7CL; all P <8.0E^-4). The SNPs associated with increased risk for DCM were also associated with increased left ventricular end-diastolic and end-systolic volumes and lower left ventricular ejection fraction among UK Biobank participants without cardiomyopathy or clinical heart failure (all P <.01). Sentinel SNPs for DCM also demonstrated a trend toward an opposite direction of association with HCM in MVP.

“These researchers have found [5] additional locations in the human genome associated with dilated cardiomyopathy that we didn’t know about before, and there’s the potential that in the future, we could develop therapies that take advantage of one or more of these genes in order to be able to provide more targeted treatment for people who have [DCM],” Dr Kiran Musunuru, AHA volunteer expert, professor of medicine, scientific director of the Penn Center for Inherited Cardiovascular Disease, and director of Genetic and Epigenetic Origins of Disease Program at the Cardiovascular Institute at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, said in an AHA news release.” In addition, there’s also the possibility that we can use this information to better predict exactly who is at risk of getting the disease and who is not at risk. Thus, it can help us identify people who need to be monitored closely . . . and then be able to provide treatment earlier.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Aragam KG, Charest B, Gaziano JM, et al. Genome-wide association study of dilated cardiomyopathy in the VA Million Veteran Program. Presented at: AHA Scientific Sessions 2021; November 13-15, 2021. Presentation 236. Analysis identified new genetic loci linked to dilated cardiomyopathy in U.S. veterans. News release. American Heart Association. November 8, 2021. Accessed November 11, 2021. https://newsroom.heart.org/news/analysis-identified-new-genetic-loci-linked-to-dilated-cardiomyopathy-in-u-s-veterans