Uncovering an Intermediate Phenotype Associated With rs2200733 at 4q25 in Lone Atrial Fibrillation

Genomewide association studies have reproducibly identified rs2200733T on chromosome 4q25 as a risk factor for the most common sustained arrhythmia, atrial fibrillation (AF). The biologic basis for cardiac electrical instability conferred by this noncoding variant is unknown. The aim of this study was to investigate potential relations between rs2200733 versus clinical and electrocardiographic traits in a cohort of patients with early-onset AF who lack traditional risk factors. Congruent with previous reports, the minor T allele was overrepresented in subjects with lone AF. All genotype groups were statistically similar for age at diagnosis, gender distribution, family history, body mass index, AF type, ventricular rate, QRS duration, corrected QT interval, and use of PR interval–prolonging medications. However, a novel association was identified between the TT genotype and duration of the PR interval. The TT group had a mean PR interval of 189.5 ± 35.8 ms in comparison to mean PR intervals of 172.0 ± 29.0 and 171.0 ± 27.1 ms for the CT and CC groups, respectively (p = 0.013 and p = 0.0056). In conclusion, PR interval length, an established risk factor for AF, represents an rs2200733-associated intermediate phenotype.