New genetic risk factor for sudden cardiac death identified
In a large and comprehensive investigation into the underlying causes of sudden cardiac death (SCD) a surreptitious killer of hundreds of thousands annually in the United States researchers have discovered a variation in the genome's DNA sequence that is linked to a significant increase in a person's risk of SCD.
The new finding flags a DNA sequence called the BAZ2B locus, a region along the genome containing three genes previously unknown to play any role in cardiac biology, according to a report published online June 30 in PLoS Genetics. Understanding how genetic variation in this region plays a role in the risk of SCD could eventually help those at risk take steps to prevent it, the researchers say, although they emphasize that a great deal of follow-up work is required.
"Our analysis suggests that if you have one copy of this variant, your increased risk is double that of someone who doesn't," says Dan Arking, Ph.D., lead author of the study and an associate professor in the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine. "If you have two copies having inherited one from each parent you have almost a fourfold increased risk of SCD."
Statistically significant though it is, this variant alone doesn't give scientists the information they need to proceed with a clinically useful test or therapy, Arking says. Scientists first need to figure out which of the three genes in the region is the key player, and determine how that gene's function is compromised likely by using model organisms to investigate their heart-related biological activity.
To identify the variant, a consortium of researchers first combined five separate genome wide association studies to survey each of the 3 billion base pairs in the DNA sequences of 1,283 individuals of European ancestry who experienced SCD, and more than 20,000 individuals without SCD. They followed up suggestive findings in an additional 3,119 SCD cases and 11,146 non-SCD control subjects from 11 European ancestry studies to confirm that the BAZ2B locus is associated with SCD.
Collecting enough DNA samples to yield statistical power has been a challenge for investigators studying SCD, Arking says. One reason is that most individuals who experience it do not have clinical signs that would suggest that they are at high-risk for SCD. In addition, only about 10 percent of people survive their initial sudden death events. (Even if the heart stops beating, a person might be saved if the heart is shocked quickly enough back into normal rhythm. The episode is still considered a sudden death event, even if the person survives, because death would have occurred without intervention.)
"SCD is a distinct disorder that involves an electrical instability in the heart," Arking says. "It's what happens when a 40-year-old guy one minute is feeling great, working out on a treadmill, and the next minute, without warning, drops dead."
Arking emphasized that based on their analyses, plenty of people are walking around with the BAZ2B variant who don't experience sudden death. SCD is a complex disease, he says, meaning this newly identified risk factor is neither necessary nor sufficient as its cause. The variant is independent of other risk factors for sudden cardiac death, which include diabetes, heart attack, and a prolonged QT interval, a measure of electrical activity in the heart obtained from a standard electrocardiogram (ECG).
"While we've done a great job of treating coronary disease and reducing the risk of heart attacks, we've made very little progress in reducing the risk of sudden cardiac death," Arking says. "The use of genetics to screen broadly is critical because we don't have other measures that will do a good job of identifying people at risk."
More information: PLoS Genetics, www.plosgenetics.o… query=arking
Provided by Johns Hopkins Medical Institutions
- Healthy lifestyle associated with low risk of sudden cardiac death in women Jul 05, 2011 | not rated yet | 0
- Feeling down and out could break your heart, literally Mar 09, 2009 | not rated yet | 0
- Sleep apnea may be risk factor for sudden cardiac death Nov 10, 2008 | not rated yet | 0
- Mayo Clinic study finds risk of sudden cardiac death highest early after attack Nov 04, 2008 | not rated yet | 0
- Scientists ID ten genes associated with a risk factor for sudden cardiac death Mar 22, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
Genetics May 22, 2013 | 4.5 / 5 (4) | 0 |
University of Minnesota Medical School researchers from the Masonic Cancer Center, University of Minnesota, in partnership with the University's Brain Tumor Program, have developed a new mouse model of malignant peripheral ...
Genetics May 20, 2013 | 5 / 5 (1) | 0 |
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | 3 / 5 (1) | 1 |
Informed consent is the backbone of patient care. Genetic testing has long required patient consent and patients have had a "right not to know" the results. However, as 21st century medicine now begins to use the tools of ...
Genetics May 16, 2013 | 5 / 5 (1) | 3 |
Ethicists provide framework supporting new recommendations on reporting incidental findings in gene sequencing
In a paper published in Science Express, a group of experts led by bioethicists in the Center for Medical Ethics and Health Policy at Baylor College of Medicine provide a framework for the new American College of Medical Geneti ...
Genetics May 16, 2013 | not rated yet | 0
(Medical Xpress)—Regulating the distribution of power in neurons is done by a system that makes the national electric grid look simple by comparison. Each neuron has several thousand mitochondria confined ...
16 minutes ago | not rated yet | 0 |
Breast cancer characterized as "triple negative" carries a poor prognosis, with limited treatment options. In some cases, chemotherapy doesn't kill the cancer cells the way it's supposed to. New research from Western University ...
27 minutes ago | not rated yet | 0
Mayo Clinic researchers have used next generation genomic analysis to determine that some of the more aggressive prostate cancer tumors have similar genetic origins, which may help in predicting cancer progression. The findings ...
31 minutes ago | not rated yet | 0
(HealthDay)—A shortage of a critical tuberculosis drug has hampered the efforts of health departments across the United States to contain the spread of the highly infectious lung disease, federal officials ...
31 minutes ago | not rated yet | 0
Maintaining a heart healthy lifestyle may also help protect chronic kidney disease patients from developing kidney failure and dying prematurely, according to a study appearing in an upcoming issue of the Journal of the Am ...
51 minutes ago | not rated yet | 0
(AP)—Merck & Co. says it is ending development of an experimental Parkinson's disease drug because the drug wasn't working.
7 minutes ago | not rated yet | 0