The genomic Distribution of eQTNs and TCs in the CEU and the YRI Populations
The tan and black boxes represent the chromosomes in the CEU (left) and the YRI (right) samples. The green tick marks denote the location of distant TCs. The yellow tick marks denote the location of local TCs. The red tick marks above the chromosome boxes denote the location of the distant eQTNs, and the red tick marks below the chromosome boxes denote the position of the local eQTNs.

ORMDL3 Gene Expression Is Associated with SNP rs1051740 in the CEU
(A) The whole-genome association of ORMDL3 expression level in the CEU population.
(B) SNP rs1051740 and SNP rs7216389 have an additive effect on the expression of ORMDL3. The red allele denotes the allele corresponding to higher gene expression level of ORMDL3, which is implicated with higher risk of asthma susceptibility in the study of Moffatt et al. 32
(C) The location of EPHX1_H113Y (rs1051740) in the conserved protein domain of EPHX1 (epoxide hydrolase N terminus, CDD:69934).

The Distantly Associated eQTN_hotspots
(A) The genomic distribution of eQTN_hotspots. The x axis represents location on the chromosome of distant eQTN_hotspots, and the y axis is the number of TCs associated with the eQTNs in each bin (bin size equals to 500 Kb). The dashed lines show the maximum number of six associated TCs that would be expected to fall into any one bin by chance with a probability of 0.001 (binomial test, corrected by the bin numbers). Bins with bar heights at or above this line represent eQTN_hotspots. There are 14 and 38 hotspots in CEU and YRI, respectively (see Table S4). Hotspots were numbered sequentially according to their locations in the genome from chromosome 1 to 22. The stars denote two distant eQTN_hotspots in the YRI associated with gene sets enriched in functional-annotation categories (details in Table 2).
(B and C) Heat maps of the expression of TCs associated with the eQTN hotspots of YRI_Hs_30 and YRI_Hs_36. The rows are TCs, and columns are the YRI samples. The green and red color in the heat map means expression below and above the average level, respectively.
(D) Heat map of the expression patterns of histone genes and their related genes in the CEU and the YRI samples. The rows are TCs, and columns are 176 samples. The green and red colors in the heat map indicate expression below and above the average level, respectively.
(E) The expression levels of histones and their related genes in the CEU (red) and YRI (blue) samples. The shading indicates an association between expression level with one or more eQTNs in CEU only (pink), in YRI only (blue), or in both (green).

Features of Significant Association in the CEU and the YRI LCLs
(A) Histogram of average expression levels of 16,997 TCs in human LCLs (176 individuals). The horizontal blue box-plot provides the mean and 95% confidence intervals of the expression levels of 16,997 TCs. The gray vertical bars represent TCs whose mean log₂-transformed expression values in 176 LCLs are less than or equal to 5.405, the 25^th quantile of mean TC expression values; the dark blue vertical bars represent the 12,747 TCs selected for the genome-wide association (GWA) study.
(B) Relationship between raw p value and false-discovery rate (FDR) of the GWA studies in the CEU and the YRI samples. The FDR values are estimated with Benjamini-Hochberg correction. There are two dashed vertical lines denoting p value of 3 × 10⁻⁶ (p value of 0.05 corrected by 12,747 tested TCs) and 2 × 10⁻⁸ (p value of 0.05 corrected by the approximately two million SNPs), respectively. p value of 2 × 10⁻⁸ corresponds to an FDR < 0.1 in the GWA studies of both CEU and YRI samples.
(C and D) The genomic distribution of 4,677 TC-eQTN associations in the CEU (C), and the genomic distribution of 5,125 TC-eQTN associations in the YRI (D). The blue crosses are the distant TC-eQTN associations; the red crosses along the diagonal lines are the local TC-eQTN associations.
(E and F) The intrapair distance distribution of 2,102 CEU (red) and 761 YRI (blue) same-chromosome TC-eQTN pairs (E). The intrapair distance distribution of 118 CEU (red) and 40 YRI (blue) same-chromosome TC-eQTN pairs having eQTNs in the conserved region (F). IPD on the x axis refers to intrapair distance.