Linkage disequilibrium (LD) is often used in genetic association studies to select tagSNPs for genotyping that represent a region in the genome. While this method is cost effective, identifying an association with a tagSNP does not necessarily identify the true functional variant given that the un-assayed functional variant is most likely in LD with the assayed variant. TagSNPs are also population specific; therefore, associations identified in one population may not necessary generalize to another population if only the index variant is genotyped. Our observations in this African American population compared with European descent populations for ECG trait associations are consistent with known properties of tagSNPs. That is, there are differences in LD between African Americans and Europeans for known loci associated with PR interval, QRS duration, and QT interval. For the SCN10A/SCN5A and NOS1AP regions, we calculated pair-wise LD (r2) for each SNP pair. As expected, there is less linkage disequilibrium in African descent populations compared to European populations (Supplementary Figs. 3 and 4) (Rosenberg et al. 2010). This lack of LD could account for the non-generalization of associations in African Americans originally identified in European descent populations.
