Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Genome-wide association studies mislead on cardiac arrhythmia risk gene

21.03.2014

Although genome-wide association studies have linked DNA variants in the gene SCN10A with increased risk for cardiac arrhythmia, efforts to determine the gene's direct influence on the heart's electrical activity have been unproductive.

Now, scientists from the University of Chicago have discovered that these SCN10A variants regulate the function of a different gene, SCN5A, which appears to be the primary gene responsible for cardiac arrhythmia risk. The SCN10A gene itself plays only a minimal role in the heart, according to the study, published in the Journal of Clinical Investigation on March 18.

"Significant effort has been invested into understanding the function of SCN10A in cardiac rhythm control, with underwhelming results," said study co-leader Ivan Moskowitz MD, PhD, associate professor of pediatrics, pathology and human genetics at the University of Chicago. "It turns out that the genetic variation within SCN10A that confers arrhythmia risk actually functions on a different gene. This study highlights the fact that DNA variation associated with disease can have regulatory impact on functional targets located a considerable distance away."

Mutations within the SCN10A gene are linked with increased risk of Brugada Syndrome, which causes cardiac arrhythmias and is a leading cause of death amongst youth in some parts of the world. Genome-wide association studies—large scale experiments that look for genetic variants across the human genome with statistical associations to certain traits or diseases—were used to identify these variants, but follow-up studies have been unable to determine their function.

Curious about previous ambiguous results, Moskowitz and his colleagues looked for other genes with links to SCN10A. First, they discovered that the region of SCN10A that conferred arrhythmia risk physically contacted a neighboring gene—SCN5A—which is well-known to have an important role in cardiac arrhythmias and sudden cardiac death. They then showed that these contacts are functional, and that by removing the implicated sequences from SCN10A, expression of SCN5A was profoundly diminished.

When they analyzed large-scale human data, the team found that the SCN10A variant originally identified for Brugada Syndrome risk was associated with lowered levels of SCN5A. But the variant had no detectable effect on the levels of SCN10A.

Taken together, the evidence suggests that any link between SCN10A and cardiac arrhythmia is due to its connection with SCN5A expression. Through the results of this study, Moskowitz believes scientists will now focus on the correct gene, SCN5A, to better understand genetic risk for cardiac arrhythmia and hopes this will lead to more accurate diagnostics and potential therapies in the future.

This study also illustrates how highly-publicized genome-wide association studies can be misleading for researchers. Study co-leader Marcelo Nobrega, PhD, an associate professor of human genetics at the University of Chicago, published a similar finding for a gene associated with obesity, on March 12th in Nature.

"Genome-wide association studies have been very successful in implicating genetic variation associated with a host of human diseases and traits," Moskowitz said. "However cases like this study demonstrate that we must be more careful to evaluate the functional target of genome-wide association study hits, before we jump to conclusions that can have costly implications for how we investigate human health and generate disease diagnostics and therapies."

###

The study, "A common genetic variant within SCN10A modulates cardiac SCN5A expression," was funded by the National Institutes of Health, the European Community's Seventh Framework Programme contract, the Cardiovascular Onderzoek Nederland, the German Foundation for Heart Research and the Federal Ministry of Education and Research. Additional authors include Malou van den Boogaard, Scott Smemo, Ozanna Burnicka-Turek, David E. Arnolds, Harmen J.G. van de Werken, Petra Klous, David McKean, Jochen D. Muehlschlegel, Julia Moosmann, Okan Toka, Xinan H. Yang, Tamara T. Koopmann, Michiel E. Adriaens, Connie R. Bezzina, Wouter de Laat, Christine Seidman, J.G. Seidman, Vincent M. Christoffels and Phil Barnett.

Kevin Jiang | EurekAlert!
Further information:
http://www.uchospitals.edu

Further reports about: Medical SCN10A arrhythmias cardiac function genome-wide levels variant

More articles from Life Sciences:

nachricht Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg

nachricht Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Physics boosts artificial intelligence methods

19.10.2017 | Physics and Astronomy

NASA team finds noxious ice cloud on saturn's moon titan

19.10.2017 | Physics and Astronomy

New procedure enables cultivation of human brain sections in the petri dish

19.10.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>