Table 4.
Functional annotations of SNPs in selected replicated 3-SNP haplotypes.
| Chr | 3-SNP haplotype | SNP | Chr position (hg19) | Ontology | Mapped gene | DHS overlapa, # EIDs (# PBC EIDs) |
H3K4me1 overlapa, # EIDs (# PBC EIDs) |
H3K4me3 overlapa, # EIDs (# PBC EIDs) | Bound proteinb: Cell line (protein) |
# Altered motifsc | Significant eQTLsd: Tissue (gene) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 6 | (rs3129881 = C) or ((rs375244 = A) and (rs3132947 = G)) | rs3129881 | 32409484 | intronic | HLA-DRA | 0 (0) | 42 (20) | 50 (17) | GM12878 (OCT2, POL2, POL24H8, POU2F2); GM12891 (OCT2, POL2, POL24H8, POU2F2); GM12892 (POL2, POL24H8) | 3 | Whole Blood (C4A, C4B, HLA-DQA1, HLA-DQA2, HLA-DQB2, HLA-DRB5); Lymphoblastoid (HLA-DQA2, HLA-DRB5); Liver (HLA-DRB5) |
| rs375244 | 32191457 | intronic | NOTCH4 | 0 (0) | 69 (15) | 38 (3) | NA | 3 | Whole Blood (GPSM3, NOTCH4) | ||
| rs3132947 | 32176782 | intronic | NOTCH4 | 0 (0) | 2 (1) | 4 (0) | NA | 3 | Whole Blood (AGPAT1, C4A, C4B, CYP21A1P, HLA-DRA, PBX2, SKIV2L); Lymphoblastoid (C4A, HLA-DQA1, RNF5); Liver (AGPAT1, RNF5) | ||
| 6 | ((rs9268831 = T) or (rs9269190 = T)) or (rs9270652 = C) | rs9268831 | 32427748 | intergenic |
HLA-DRA (dist = 14922), HLA-DRB5 (dist = 57406) |
5 (1) | 31 (19) | 71 (16) | GM18951 (POL2) | 1 | Whole Blood (HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB1-AS1, HLA-DQB2, HLA-DRB1, HLA-DRB6, HLA-DRB9); Lymphoblastoid (HLA-DQA2, HLA-DQB2, HLA-DRB6, HLA-DRB9, NOTCH4); Liver (HLA-DQA2, HLA-DQB2) |
| rs9269190 | 32448500 | intergenic |
HLA-DRA (dist = 35674), HLA-DRB5 (dist = 36654) |
2 (2) | 4 (4) | 2 (2) | NA | 2 | Whole Blood (HLA-DRA) | ||
| rs9270652 | 32565905 | intergenic |
HLA-DRB1 (dist = 8292), HLA-DQA1 (dist = 39278) |
1 (1) | 1 (1) | 2 (0) | NA | 0 | NA | ||
| 6 | (rs9295704 = C) and ((rs2451752 = A) and (rs2575174 = C)) | rs9295704e | 26704816 | intergenic | ZNF322 (dist = 44836), GUSBP2 (dist = 134450) | 0 (0) | 13 (1) | 8 (1) | NA | 4 | Whole Blood (ABT1) |
| rs2451752e | 26648013 | intronic | ZNF322 | 0 (0) | 1 (1) | 3 (1) | NA | 0 | Whole Blood (BTN3A1, BTN3A2, HMGN4, ZNF322) | ||
| rs2575174e | 25885552 | intergenic |
SLC17A3 (dist = 11081), SLC17A2 (dist = 27432) |
0 (0) | 5 (0) | 0 (0) | NA | 2 | Whole Blood (HIST1H1T, HIST1H4A) | ||
| 7 | ((rs12671658 = T) or (rs12702656 = A)) and (rs11768586 = G) | rs12671658e | 7842281 | intronic | UMAD1 | 1 (0) | 6 (0) | 2 (0) | NA | 7 | NA |
| rs12702656e | 7851742 | intronic | UMAD1 | 0 (0) | 9 (3) | 0 (0) | NA | 4 | NA | ||
| rs11768586e | 7849806 | intronic | UMAD1 | 1 (0) | 6 (2) | 1 (1) | NA | 0 | NA | ||
| 9 | (rs4979484 = C) or ((rs13300483 = T) and (rs7028891 = G)) | rs4979484e | 117751450 | intergenic |
TNFSF8 (dist = 58575), TNC (dist = 30404) |
22 (6) | 33 (20) | 11 (7) | GM12878 (BATF, NFKB); GM12891 (NFKB); GM15510 (NFKB); GM18951 (NFKB) |
3 | NA |
| rs13300483e | 117643362 | intergenic |
TNFSF15 (dist = 74954), TNFSF8 (dist = 12261) |
0 (0) | 11 (6) | 2 (0) | NA | 2 | Whole Blood (TNFSF8) | ||
| rs7028891e | 117645015 | intergenic |
TNFSF15 (dist = 76607), TNFSF8 (dist = 10608) |
0 (0) | 4 (3) | 1 (1) | NA | 3 | Whole Blood (TNFSF8) |
Abbreviations: EID, epigenome identifier; dist, distance; #, number; DHS, DNase I hypersensitivity site; eQTL, expression quantitative trait loci.
aCounts of the number of consolidated cell types (EIDs) for which the SNP of interest overlaps the queried epigenomic assay peak (Roadmap Epigenomics Mapping Consortium processed data, Kundaje et al.)21. “PBC EID”: Separately considers peak overlap counts among the 29 blood/liver cell types available in Roadmap Epigenomics.
bBound protein: Regulatory protein-binding ChIP-seq peak overlaps for specified proteins are provided for blood- or liver-related cell lines only (HaploReg v4, Ward and Kellis)37.
cAltered motifs: The number of regulatory motifs predicted to be affected by the SNP based on position weight matrices (PWM) score changes (HaploReg v4, Ward and Kellis)37.
deQTLs: Reported significant eQTLs for whole blood, lymphoblastoid, and liver cell types only (GTEx Consortium20; HaploReg v4, Ward and Kellis)37.
eSignifies non-HLA SNPs.