Understanding Genetic Risk of Atrial Fibrillation
The key to developing a clinically useful DNA-based test for risk of atrial fibrillation (AF) is the identification of common genetic variants that confer significantly increased risk of the condition. deCODE AF™ detects the first two SNPs that meet this criteria and that have been shown to confer risk in multiple populations.
To identify genetic variants conferring risk of AF in the general population, deCODE conducted a genome-wide analysis of more than 300,000 SNPs across the entire genome in a cohort of a total of 5,000 Icelandic AF patients and healthy controls. Alleles (bases) of two SNPs, rs2200733 and rs100233464, both located near the PITX2 gene on chromosome 4q25, were found to be significantly more common in AF patients than in control subjects. The PITX2 gene is known to play a role in cardiac development.
These findings were then validated in studies of a total of more than 18,000
patients with all forms of AF and controls, including cohorts from Iceland,
Sweden, the Massachusetts General Hospital in Boston, and, for the strongest
of the variants, a cohort of Han Chinese from Hong Kong. The deCODE AF test
measures the at-risk versions of these two SNPs. Approximately 30% of those
of European ancestry in deCODE’s studies are positive for the deCODE AF™
test, corresponding to an average 2-fold increase in likelihood of AF compared
to those negative for the test.