2022 AHA/ACC/HFSA Guideline for the Management of Heart ...
Study Uncovers Genetic Risk Factors For Heart Failure
In a new study co-led by investigators at the United States Department of Veterans Affairs and Brigham and Women's Hospital, a founding member of the Mass General Brigham health care system, a global team of scientists conducted one of the largest genetic association studies on heart failure to date. Using genomic data from over 90,000 heart failure patients and more than a million controls, the team identified 39 genetic mutations associated with heart failure, 18 of which had not been reported previously.
The researchers also pinpointed seven druggable proteins that, when targeted with specially designed medications, may prevent heart failure's onset. They say their overall findings, published today in Nature Communications, could one day help physicians identify and treat at-risk patients before heart failure occurs.
"Our study provides a better understanding of disease etiology, identifies causal pathways, and pinpoints potential drug targets for the primary prevention of heart failure," said lead author Danielle Rasooly, Ph.D., a research associate in the Brigham's Department of Medicine. Rasooly is also an investigator for the VA's Million Veteran Program.
Heart failure affects over 60 million people worldwide and 6 million people in the United States, costing the American health care system over 30 billion dollars every year. Patients diagnosed with heart failure have an estimated five-year survival rate of 50%, which has pressed scientists to better understand the environmental and genetic risk factors associated with heart failure.
Although several studies in the past decade have used advanced computing techniques to identify genetic risk factors for heart failure, scientists have wondered if their limited sample sizes have allowed some unidentified mutations to slip through the cracks. Genome-Wide Association Studies (GWAS), which look for differences in the DNA of patients with diseases and healthy controls, are only as comprehensive as the datasets they're built on.
GWAS with larger sample sizes have more statistical power, meaning they're able to find mutations that smaller-cohort studies may miss.
The team built their large cohort by gathering genomes from two established genomic research programs. The Million Veteran Program (MVP), a national effort launched in 2011 to examine the long-term health outcomes of United States Veterans, provided 302,287 genomes for the study. Heart failure is a particular concern for veterans, with some studies showing that they may be at a higher risk of developing heart disease. To date, over 950,000 veterans have enrolled in MVP.
"We want to thank all the veterans who have taken part in the MVP and allowed us to study how genes affect heart failure," Rasooly said.
The remaining 977,323 genomes were pulled from the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) consortium, which includes data from patients across several European countries. In total, the team analyzed 1,279,610 genome samples, 90,653 of which belonged to patients with heart failure.
Such a large dataset allowed Brigham and Veterans Association researchers to uncover 38 genetic mutants, or variants, that were associated with the presence of heart failure. Eighteen of those variants had not been previously reported as heart failure risk factors by smaller GWAS studies.
Investigators then conducted a technique called Mendelian randomization, which computationally simulates how certain interventions may affect disease outcomes. They searched for the genetic signatures of proteins that, when either increased or decreased in individuals in their dataset, led to lower risk of heart failure. Their approach heralded seven druggable proteins among nearly 5,000 candidates that they believe can be targeted to lower an individual's risk of developing heart disease.
The team says that their findings, coupled with future analyses to better understand the genetic determinants of heart failure, could one day empower physicians to predict whether a patient's unique genetic profile puts them at higher odds of developing heart failure during their lifetime. Drugmakers could also use the team's research to narrow down which proteins they should target in order to build drugs that minimize the risk of developing heart failure.
"It's well known that over 95% of clinical trials fail, and I think the techniques we leverage in this study can decrease this failure rate," Rasooly said. "Drug targets identified through genetics have at least twice the odds of success in drug discovery."
More information: Danielle Rasooly et al, Genome-wide association analysis and Mendelian randomization proteomics identify drug targets for heart failure, Nature Communications (2023). DOI: 10.1038/s41467-023-39253-3
Citation: Study uncovers genetic risk factors for heart failure (2023, August 24) retrieved 27 August 2023 from https://medicalxpress.Com/news/2023-08-uncovers-genetic-factors-heart-failure.Html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
Genetic Testing Before Pregnancy: What You Need To Know
"We can now screen for over 500 different types of [disorders] depending on the company or test you are using," says Dr. Keegan. "This gives us the opportunity to prevent the transmission of inherited genetic disorders through the technology available and a simple blood test."
The ACOG recommends considering family history and ethnicity, in addition to the most common genetic conditions, when deciding which mutations to include. Parents may also benefit from genetic counseling, which is a service that helps people understand the results of their tests and make informed decisions throughout the process.
Here are some of the most common conditions identified through genetic carrier screening:
Cystic FibrosisThere are currently almost 40,000 children and adults living with cystic fibrosis in the U.S . Cystic fibrosis is a disease that affects the lungs, pancreas and other organs. People who have cystic fibrosis have difficulties breathing. The mutation involved with cystic fibrosis causes a protein to not function correctly, which then causes mucus buildup in multiple organs throughout the body.
Fragile X SyndromeAbout 1 in 7,000 males and about 1 in 11,000 females have fragile X syndrome, the most common cause of inherited intellectual disability . Fragile X is associated with lower than average IQ, developmental delays and other co-occurring health conditions including seizures, autism, hyperactivity, attention difficulties and more.
Spinal Muscular Atrophy (SMA)One in every 6,000 babies is born with spinal muscular atrophy, or SMA, which is a group of genetic disorders that cause a weakening of the muscles . Symptoms may vary, but people with SMA may require physical and occupational therapy, support devices such as wheelchairs or assistance with breathing. Symptoms generally worsen over time and there is no cure.
Tay-Sachs DiseaseAlthough anyone can be a carrier, Tay-Sachs disease is more common for people of Ashkenazi Jewish ancestry, as one in every 27 members of the population is a carrier for the disease . Symptoms may include deafness, blindness, seizures, decreased muscle tone, dementia and others.
Sickle Cell DiseaseIt is estimated that approximately 100,000 people in the U.S. Have sickle cell disease . This inherited condition is most common in Black or African American people but can affect any race. Sickle cell disease includes a group of red blood cell disorders that can cause acute chest syndrome, anemia, blood clots or infections.
These Genetic Tests Are Now Part Of Tricare's Covered Benefits
Defense health officials have added six preconception and prenatal genetic tests to military members' health care benefits.
The lab tests that are now a Tricare covered medical benefit include one test per condition, per lifetime, for these genetic disorders:
The tests are approved retroactively back to Dec. 27, 2021, when a law went into effect specifying they would become part of Tricare's basic coverage. So, beneficiaries who have paid out of pocket for one of these screenings since that date can apply for reimbursement by contacting their Tricare regional contractor. Beneficiaries can also request that Tricare reprocess a claim that had been denied for a test during that time. The new policy took effect July 19.
"Preconception and prenatal carrier screenings help identify people at risk for having children with genetic conditions that may have a high level of death or a shortened life expectancy," said LaChanda Black, a Tricare management and program analyst, in a statement accompanying the Defense Health Agency announcement. "Providing families access to these screenings can help them make decisions when planning their family."
These six tests were previously part of the Laboratory Developed Tests Demonstration Project, but have been moved to become part of the Tricare benefit.
The demonstration project includes many other tests, however, and has been extended for another five years, through July 18, 2028. The program gives Tricare beneficiaries access to certain tests that aren't yet approved by the Food and Drug Administration.
According to a July 13 notice in the Federal Register, Defense Health Agency officials cite "an ever-expanding pool of non-FDA-approved LDTs, including tests for cancer risk, diagnosis and treatment; blood and clotting disorders; a variety of genetic diseases and syndromes; and neurological conditions."
Officials note that in some instances, "LDTs are important and necessary tests and, in many instances, there are no FDA-approved/cleared alternatives."
The agency started the demonstration project in 2014 to review non-FDA-approved laboratory developed tests to determine if they meet Tricare's requirements for safety and effectiveness, and otherwise meet Tricar's criteria for coverage. During the demonstration, DHA allows tests that meet such criteria to be covered as a benefit.
The project has been extended several times.
The non-FDA-approved tests covered under the demonstration are available under cost-sharing for eligible Tricare beneficiaries, but they must be performed by a laboratory that is assessed and certified or accredited under minimum quality standards set by the Centers for Medicare and Medicaid Services.
Beneficiaries should check with their provider or regional contractor to find out what tests are included in the demonstration.
The cost to extend the demonstration project for another five years is expected to total about $199 million, according to the Federal Register notice.
Karen has covered military families, quality of life and consumer issues for Military Times for more than 30 years, and is co-author of a chapter on media coverage of military families in the book "A Battle Plan for Supporting Military Families." She previously worked for newspapers in Guam, Norfolk, Jacksonville, Fla., and Athens, Ga.
Share:
Comments
Post a Comment