June 7, 2012

Common genetic signals for atrial fibrillation decoded

Common genetic signals for atrial fibrillation decoded

Atrial fibrillation (AF), the most commonly diagnosed abnormal heart rhythm, develops later in life and significantly increases the risk for stroke, dementia, heart failure and death, yet its genetic underpinnings remain largely a mystery.

Now an international study co-led by researchers at Vanderbilt University has uncovered six new “susceptibility loci,” chromosomal regions located in or near genes that may play a role in the disease. Three susceptibility loci had been identified previously.

“The next step for us is to study these genes and determine not only how they cause atrial fibrillation but also learn something about the biology of the arrhythmia,” said Dawood Darbar, M.D., one of the lead investigators of the study, which was reported online in the journal Nature Genetics.

Dawood Darbar, M.D.

Dawood Darbar, M.D.

Eventually this knowledge may help physicians “personalize” the diagnosis and treatment of AF, said Darbar, director of the Vanderbilt Arrhythmia Service and associate professor of Medicine.

Genetic information from impressively large cohorts, or groups, of individuals of European decent was used to identify the loci, each of which contained variations in the genetic code, called single nucleotide polymorphisms (SNPs).

The six SNPs, in turn, were found using a genome-wide association study, which can determine whether common genetic variations are associated with specific traits or diseases. They were found in or near genes related to cardiac development or physiology, making them likely candidates to play a role in AF.

“Now that we have identified nine susceptibility loci, we can study a group of patients who do not have AF, determine if they carry these SNPs, and assess if they also have other risk factors for AF such as hypertension, diabetes, coronary artery disease or heart failure,” Darbar said.

“We can predict which patients are likely to develop AF in the future,” he continued. “We could even start to treat those patients at highest risk with medications that may delay or prevent the development of AF.”

Knowing a patient’s genotype may also help determine which treatment will be most effective. In another recent paper, Babar Parvez, M.D., Darbar, and their colleagues found that patients carrying one of the common AF SNPs were less responsive to anti-arrhythmic drugs that are often used to treat AF.

With six new loci to investigate, they hope to determine whether patients who carry certain SNPs respond better to certain forms of treatment for AF.

This could help physicians tailor therapies to each patient’s genotype, and could lead to the discovery of new treatments for AF.

The new findings also may help researchers answer an old question: why African-Americans are only about half as likely as Europeans to develop AF, even though the two groups have roughly similar risk factors. Darbar and his colleagues think the differences are based on genetics, and look forward to obtaining cohorts large enough to make the comparison in the near future.

Other contributing authors from Vanderbilt were Parvez and Raafia Muhammad, M.D., fellows in Cardiovascular Medicine, and Dan Roden, M.D., assistant vice chancellor for Personalized Medicine.

Vanderbilt’s contribution to the study was supported by National Institutes of Health grants 5U19HL065962 and 5R01HL092217.