Genetic variation in the rhythmonome: ethnic variation and haplotype structure in candidate genes for arrhythmias

The 'rhythmonome' is the term we have adopted to describe the set of genes that determine the normal coordinated electrical activity in the heart. Elements of this set include pore-forming ion channels, function-modifying proteins and intracellular calcium control elements. Rare mutations in many of these genes are known to cause unusual congenital monogenic arrhythmia syndromes, and single common variants have been reported to modify arrhythmia phenotypes. Here, we report an evaluation of the variation and haplotype structure in six key components of the rhythmonome.

SNPs were typed using DNA extracted from Coriell cell lines to survey allele frequencies and haplotype structure in six genes (ANK2, SCN5A, KCNE1 and 2 gene cluster, KCNQ1, KCNH2 and RYR2) across four human populations (African-American, European American, Han Chinese and Mexican American).

A total of 307 SNPs were analyzed across the six genes, revealing significant allele-frequency differences between populations and clear differences in haplotype structure.

The pattern of variation we report is an important step towards incorporating common variation across the rhythmonome in studies of arrhythmia susceptibility.