Connecting the Dots in Atrial Fibrillation.

Atrial fibrillation is a common cardiac arrhythmia displaying a large heritable component,1 with twin studies estimating the genetic heritability at ≈60%.2 Several genome-wide association studies have been performed to identify common DNA variation associated with risk for disease and have to date identified 23 genomic loci with genome-wide significance.3 Each of these loci contains several common single-nucleotide polymorphisms (SNPs) that are significantly associated with disease risk, lie almost exclusively in nonprotein-coding regions of the human genome, and whose potential effects on surrounding protein-coding genes are largely unknown. The biggest challenge in postgenomic studies therefore lies in the functional annotation of those SNPs and the identification of the downstream target genes. See Article by Tucker and Dolmatova et al In this issue of Circulation: Cardiovascular Genetics , Tucker et al4 elegantly link noncoding variation via enhancer function with a disease phenotype (Figure) at …