Table 2.
Prioritized Variants of the Giant Cell Arteritis-Associated Non-HLA Regions Accordingly to the Functional Annotations of the Lead Signals and Their Proxies using ENCODE Data
| SNP | Location (GRCh37) | Locus | Distance from Hit (bp) | r2 | RDB Score |
Regulatory Chromatin Marks |
Protein Binding and Regulatory Motifs |
GRASP QTL and eQTL Annotations |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Promoter Histone Marks | Enhancer Histone Marks | DNase Hypersensitivity | Proteins Bound (ChIP-Seq) | Regulatory Motifs Altered (PWM) | GRASP QTL Traits | p Value | Ref (PMID) | eQTL Hits | ||||||
| rs4252134 | 6:161153527 | PLG (intronic) | 0 | NA | 6 | – | – | – | – | – | gene expression of DDR1 in peripheral blood monocytes | 3.31 × 10−6 | 20502693 | – |
| rs4252126 | 6:161152294 | PLG (intronic) | 1,233 | 0.995 | 1f | yes | – | yes | CTCF | Pax-6 | – | – | – | – |
| rs4252135 | 6:161154232 | PLG (intronic) | 705 | 1.000 | 1f | yes | yes∗ | yes∗ | CTCF, RAD21, SMC3, ZNF143, NFKB, FOXA1, FOXA2, ZNF263 | COMP1 | gene expression of DDR1 in peripheral blood monocytes | 2.92 × 10−6 | 20502693 | – |
| rs34126283 | 6:161130002 | PLG (intronic) | 23,525 | 0.920 | 3a | yes | yes | yes | GATA2 | Cdc5, E2F, Evi-1, HDAC2, PLZF, Pou2f2, TATA | – | – | – | – |
| rs4252125 | 6:161152240 | PLG (missense) | 1,287 | 0.995 | 3a | yes | – | yes | CTCF, RAD21 | AP-3 | gene expression of UNQ9391 in liver | 4.09 × 10−14 | 22006096 | – |
| rs128738 | 5:131540875 | P4HA2 (intronic) | 0 | NA | ND | yes | yes∗ | – | – | BDP1 | – | – | – | 24 |
| rs101194 | 5:131515413 | P4HA2 (intergenic) | 25,462 | 0.901 | 3a | yes | yes∗ | yes | GATA2, P300 | CEBPB | gene expression of P4HA2 in lymphoblastoid cell lines | 2.00 × 10−7 | 17873874 | 30 |
| gene expression of SLC22A5 in peripheral blood monocytes | 1.16 × 10−8 | 20502693 | – | |||||||||||
| rs152054 | 5:131519540 | P4HA2 (intergenic) | 21,335 | 0.967 | 3a | yes∗ | yes∗ | yes∗ | CFOS | BAF155, BCL, Egr-1, Ets, FEV, GATA, NERF1a, Nrf-2, PU.1, Pax-5, SETDB1, SIX5, Tel2, Znf143 | – | – | – | 25 |
| rs152051 | 5:131539025 | P4HA2 (intronic) | 1,850 | 1.000 | 3a | yes | yes∗ | yes∗ | YY1, NFKB | AIRE, Foxa, GR, VDR | gene expression of P4HA2 in CEU-CHB-JPT-YRI lymphoblastoid cell lines | 4.66 × 10−9 | 17873874 | 28 |
| rs156023 | 5:131545168 | P4HA2 (intronic) | 4,293 | 0.967 | 3a | yes∗ | yes∗ | – | – | AIRE, LBP-1, LBP-9 | – | – | – | 22 |
Chromatin marks in blood tissues are indicated with an asterisk. Abbreviations are as follows: SNP, single nucleotide polymorphism; GRCh37, genome reference consortium human genome build 37; bp, base pair; RDB, Regulome database; PWM, position weight matrix ID; GRASP, genome-wide repository of associations between SNPs and phenotypes; PMID, PubMed identifier; eQTL, expression quantitative trait loci. RDB scores: 1f, eQTL + TF binding / DNase peak; 3a, TF binding + any motif + DNase peak; 6, other; ND, no data; NA, not applicable.