Scientists at deCODE genetics and colleagues from Europe and the US reported on 14 July the discovery of a common single-letter variant in the sequence of the human genome (SNP) conferring increased risk of atrial fibrillation (AF) and stroke.
The findings will be integrated directly into the deCODE AF reference laboratory test for gauging individual risk of AF and stroke and helping to identify stroke patients who may benefit from enhanced monitoring for AF. The study is published online in Nature Genetics at www.nature.com/ng.
The new SNP is in the ZFHX3 gene on chromosome 16q22, and the more than one third of people of European descent who carry one copy are at approximately 20% greater risk of AF and cardioembolic stroke than are individuals who carry none. Because AF is often intermittent and difficult to detect, gauging genetic susceptibility can help doctors to decide which of their stroke patients might benefit from longer-term monitoring for AF following a stroke. Those with stroke due to AF may be given different therapy than they would otherwise. This is the purpose of deCODE AF, at the heart of which is the major AF and stroke variant discovered by deCODE on 4q25. Indeed the findings are the result of deCODE’s program to build on this work and to find new risk variants. After expanding their genome-wide association study in Iceland, the deCODE team took the top SNPs outside the 4q25 region and typed them in case-control cohorts from Iceland, Norway and the US. This confirmed the ZFHX3 SNP as a risk variant for AF. Analysis in stroke cohorts from Iceland, Germany, Sweden and the UK demonstrated that this SNP was associated with increased risk of stroke, particularly cardioembolic stroke.
Financial support for this study was provided by US National Institutes of Health, American Heart Association, German Federal Ministry of Education and Research, German Migraine & Headache Society, Astra Zeneca, Berlin Chemie, Boots Healthcare, Glaxo-Smith-Kline, McNeil Pharma, MSD Sharp & Dohme and Pfizer to the University of Muenster.