as well as an association with atrial arrhythmias.10 The top association in a GWAS of normal cardiac conduction (assessed by variability in QRS durations on normal ECGs) was in a sodium channel gene SCN10A, and PheWAS demonstrated that the top SNP was associated with atrial fibrillation, developing over years after the initial normal ECG.39 After these initial studies demonstrated feasibility of the approach, 3,144 PheWAS using GWAS data across eMERGE sites analyzed SNPs previously identified as potential mediators of disease susceptibility or other physiologic traits in 1,358 EHR derived phenotypes across 13,835 individuals.41 This study replicated 51 out of 77 sufficiently powered prior GWAS associations, showing PheWAS can be used as a replication tool to complement other genetic association studies. Others have used EHR-based PheWAS approaches to replicate new associations,42 to identify functional variants,42 highlight potential drug targets,43 and to identify signals in multiethnic populations.44
