Fig 1.
puQTL mapping using RNA-seq data.
(A) Schematic view of eQTL and puQTL mapping. (B) Pipeline for puQTL mapping. 1KGP, the 1000 Genomes Project; MAF, minor allele frequency; GTF, gene transfer format. (C) Quantile–quantile plot of P-values. The nominal pass results of chromosome 22 are plotted, and the red line indicates the expected P-values under the null hypothesis. (D) Distribution of the distance of puQTL best hit variants from the target promoters. (E) Overlap of puQTL genes and eQTL genes. (F) Counts of puQTL associated with multi-promoter genes based on categories of proximity to their target promoters. “Nearest” means that the puQTL targets the nearest promoters of the associated genes, “2nd” means that they target the second nearest promoters, and so forth.
Fig 2.
Enrichment of epigenetic features.
(A) Aggregation plots of histone mark ChIP-seq and ATAC-seq signals for the 100 kb regions flanking puQTL best hit variants. (B–E) Enrichment of the peaks of histone mark ChIP-seq and transcription factor footprints at puQTL (B) and eQTL (C), and enrichment of the chromatin states defined by ChromHMM at puQTL (D) and eQTL (E). The red dots represent significant enrichment at the 5% FDR level, and the bars indicate 95% confidence intervals.
Fig 3.
puQTL-associated gene classification.
(A) The procedure used for puQTL gene classification. (B) Count of each group of puQTL genes. (C) The TMEM200A gene locus. The structures of the TMEM200A gene in the Ensembl 104 annotation and assembled in this study are presented in black and red, respectively, with ENCODE GM12878 H3K4me3 and H3K27ac ChIP-seq signals. The vertical blue bars indicate the location of active promoters. The black bar indicates the location of the rs11154537 variant. (D, E) Comparison of the promoter activities (D) and total expression levels (E) of the TMEM200A gene among the rs11154537 genotypes. The numbers in parentheses indicate sample size. (F) The associations of puQTL, fine-mapped puQTL for prmtr.94867, and eQTL for TMEM200A are shown in the top, middle, and bottom panels. rs11154537 is plotted in a red diamond, and the colors indicate the r-squared values between rs11154537 and other variants. (G) The SYNJ2BP-COX16 gene locus. (H, I) The promoter activities (H) and total expression levels (I) of the SYNJ2BP-COX16 gene were compared among the rs145415365 genotypes. (J) Associations of puQTL, fine-mapped puQTL for prmtr.136781, and eQTL for SYNJ2BP-COX16 are shown in the top, middle, and bottom panels.
Fig 4.
(A) The TMBIM1 gene locus. Structures of the TMBIM1 assembled in this study are presented in black with ENCODE GM12878 H3K4me3 and H3K27ac ChIP-seq signals. The isoforms transcribed from prmtr.64998 are shown in red. The vertical blue bars indicate the location of active promoters. The black bar indicates the location of the rs2382817 variant. (B, C) Comparison of the promoter activities (B) and total expression levels (C) of the TMBIM1 gene among the rs2382817 genotypes. The numbers in parentheses indicate sample size. (D) The associations of puQTL, fine-mapped puQTL for prmtr.64998, eQTL for TMBIM1, and GWAS of inflammatory bowel disease (IBD) are shown from the top to bottom panels. rs2382817 is plotted in a red diamond, and the colors indicate r-squared values between rs2382817 and other variants. (E) The MAPKAP1 gene locus. The structures of the MAPKAP1 gene assembled in this study are presented in black, and the isoforms transcribed from prmtr.109751 are shown in red. (F, G) Comparison of the promoter activities (F) and total expression levels (G) of the MAPKAP1 gene among the rs631287 genotypes. (H) The associations of puQTL, fine-mapped puQTL for prmtr.109751, eQTL for MAPKAP1, and GWAS of diverticular disease are shown from the top to bottom panels.