Toward Multiple SNP Motif Analyses of Loci Associated With Phenotypic Traits

A recent paper in the Journal (1) and other studies (2) are greatly improving our overview of candidate genetic codeterminants of cardiovascular risk or blood pressure and are also raising curiosity about sources of consistently strong (e.g., p < 10−15) observed associations. In 12q24, a single nucleotide polymorphism (SNP) (rs3184504) (1) in 1 of 6 loci associated with coronary artery disease was also strongly associated with blood pressure (2); an Internet summary (3) noted its associations with 17 diseases or disease-related characteristics.

From the 1000 Genomes Project Consortium (4), we extracted 15 SNPs, <30-kb haplotype-motif views around rs3184504 for individual and pooled world populations. The world view revealed strong population structure of the 15-SNP motifs (Figure 1) (n = 2 × 2,504 haplotypes). At least 2 of the giant components and their master motifs (H1 to H4; encoded as in the 1000 Genomes Project Consortium study) (4) also appeared in individual populations, including some (e.g., Great Britain, GBR) that are generally not considered appreciably admixed or structured. Two dominating consensus motifs (H1+H2+H4 and H3) account for 83% of the 5,008 haplotypes worldwide.