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

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