Navigation Links
Genome-wide association studies mislead on cardiac arrhythmia risk gene
Date:3/20/2014

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 studieslarge scale experiments that look for genetic variants across the human genome with statistical associations to certain traits or diseaseswere 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 geneSCN5Awhich 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."


'/>"/>

Contact: Kevin Jiang
kevin.jiang@uchospitals.edu
773-795-5227
University of Chicago Medical Center
Source:Eurekalert

Related biology news :

1. Genome-wide imaging study identifies new gene associated with Alzheimers plaques
2. 23andMe identifies 5 significant genetic associations for hypothyroidism
3. Amarantus BioSciences to Present at the National Investment Banking Associations (NIBA)122nd Conference in New York City
4. American Association for the Advancement of Science - Pacific Division convenes in Boise June 24-27
5. New research association started: Magnesium implants shall facilitate bone fracture healing
6. Pioneering researcher receives Heart Association Lifetime Achievement Award
7. Researchers sequence swine genome, discover associations that may advance animal and human health
8. Kansas State University scientists named American Association for the Advancement of Science fellows
9. UMass Medical School faculty elected to the American Association for the Advancement of Science
10. Association of Environmental Engineering and Science Professors name Environmental Engineering Science as its official journal
11. NREL employees honored by industry associations
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/28/2016)... 28, 2016 First quarter 2016:   ... compared with the first quarter of 2015 The gross ... M (loss: 18.8) and the operating margin was 40% (-13) ... Cash flow from operations was SEK 249.9 M (21.2) , ... is unchanged, SEK 7,000-8,500 M. The operating margin for ...
(Date:4/15/2016)... April 15, 2016  A new partnership announced ... accurate underwriting decisions in a fraction of the ... priced and high-value life insurance policies to consumers ... With Force Diagnostics, rapid testing (A1C, Cotinine ... readings (blood pressure, weight, pulse, BMI, and activity ...
(Date:3/31/2016)...   LegacyXChange, Inc. ... LegacyXChange is excited to release its first ... be launched online site for trading 100% guaranteed authentic ... also provide potential shareholders a sense of the value ... industry that is notorious for fraud. The video is ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... /PRNewswire/ - FACIT has announced the creation of ... company, Propellon Therapeutics Inc. ("Propellon" or "the Company"), ... portfolio of first-in-class WDR5 inhibitors for the treatment ... represent an exciting class of therapies, possessing the ... cancer patients. Substantial advances have been achieved with ...
(Date:6/23/2016)... MONICA, Calif. , June 23, 2016  The Prostate Cancer Foundation ... pioneer increasingly precise treatments and faster cures for prostate cancer. Members of the ... institutions across 15 countries. Read More About the Class ... ... ...
(Date:6/23/2016)... ... June 23, 2016 , ... STACS DNA Inc., the sample ... the Arkansas State Crime Laboratory, has joined STACS DNA as a Field Application Specialist. ... said Jocelyn Tremblay, President and COO of STACS DNA. “In further expanding our capacity ...
(Date:6/23/2016)... 2016 Andrew D ... http://doi.org/10.17925/OHR.2016.12.01.22 Published recently in ... from touchONCOLOGY, Andrew D Zelenetz , discusses ... care is placing an increasing burden on healthcare ... therapies. With the patents on many biologics expiring, ...
Breaking Biology Technology: