Effect of individual SNPs in multiple enhancer variant loci. (A) Schematic describing “imperfect LD” loci. When SNPs are in perfect LD, the lead GWAS SNP is indicative of the genotype of the entire allele and the locus includes only two haplotypes (red and purple) and three possible genotypes (red/red, red/purple, purple/purple). For loci with “imperfect LD” the lead SNP does not predict the genotype of remaining SNPs. This results in more than two haplotypes and more than three genotypes. (B) Percent of GWAS loci associated with transcripts that show differential gene expression based on SNP genotype for multiple enhancer variant loci in sites of “imperfect LD” (black) and perfect LD (red), Fisher's exact test. (C) Expression of predicted gene target (PFKFB3) of an “imperfect LD” locus which contains the RA-associated SNP rs706778. Individuals are stratified based on the genotype of each LD SNP that falls within an enhancer. (D) Each individual is color-coded based on his or her haplotype for the rs706778 “imperfect LD” locus (middle). Note that the expression of the predicted target gene PFKFB3 segregates by haplotype only when the multiple enhancer variants are in tight LD (right) (Mann-Whitney-Wilcoxon test). (E) Standard deviation of expression of predicted gene targets within multiple enhancer variant loci with “imperfect LD” for individuals stratified by lead SNP genotype (black) and stratified by haplotype (red) (Mann-Whitney-Wilcoxon test). (F) Odds ratios for multiple enhancer variant loci showing perfect (red) and imperfect LD (black) (Welch's t-test). (*) P < 0.04, (**) P < 0.009.