HelmholtzZentrum munich
WCMC

Connecting genetic risk to disease endpoints through the human blood plasma proteome

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 48

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
ILT-4 cis Discovery rs103294 19:54,797,848 C/T 0.19 995 -0.943 0.048 1.7×10-73 -1.230 3.6×10-80 2.8×10-64
ILT-4 cis Replication rs798888 19:54,793,239 G/A 0.13 337 -0.832 0.089 1×10-18 -1.300 1.7×10-16 7.7×10-10

 

Regional association plots

Leukocyte immunoglobulin-like receptor subfamily B member 2 (ILT-4)

 

Boxplots and histograms for top associations

Leukocyte immunoglobulin-like receptor subfamily B member 2 (ILT-4)

inverse-normalized probe levels log2 transformed probe levels raw probe levels
Discovery study
Replication study

Leukocyte immunoglobulin-like receptor subfamily B member 2 (ILT-4)

Target (abbrv.) ILT-4
Target (full name) Leukocyte immunoglobulin-like receptor subfamily B member 2
Somalogic ID (Sequence ID) SL005191 (5091-28_3)
Entrez Gene Symbol LILRB2
UniProt ID Q8N423
UniProt Comment
  • Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C and HLA-G alleles. Involved in the down-regulation of the immune response and the development of tolerance. Competes with CD8A for binding to class I MHC antigens. Inhibits FCGR1A-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions.
Reactome
  • Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

All locus annotations are based on the sentinel SNP (rs103294) and 24 proxy variant(s) that is/are in linkage disequilibrium r2 ≥ 0.8. Linkage disequilibrium is based on data from the 1000 Genomes Project, phase 3 version 5, European population and was retrieved using SNiPA's Block Annotation feature.
Download the detailed results of SNiPA's block annotation (PDF)

Linked genes

Genes hit or close-by
Potentially regulated genes
eQTL genes
  • TSEN34 TSEN34 tRNA splicing endonuclease subunit
  • LILRB2 leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 2
  • AC010518.2
  • ITIH6 inter-alpha-trypsin inhibitor heavy chain family, member 6
  • LILRA1 leukocyte immunoglobulin-like receptor, subfamily A (with TM domain), member 1

 

Results from other genome-wide association studies

Trait P Study Source
Gene expression of LILRA3 in peripheral blood monocytes 0×10-324 20502693 (PMID) GRASP2 eQTL
Gene expression of LILRA3///LILRA1 in blood 9.8×10-198 21829388 (PMID) GRASP2 eQTL
Gene expression of LILRA3 in blood 3.5×10-157 21829388 (PMID) GRASP2 eQTL
LILRA3 gene expression 1.1×10-48 21798870 (PMID) GRASP2 eQTL
HDL cholesterol 4×10-30 24097068 (PMID) Supplemental file
Gene expression of LILRA5 in blood 1.2×10-22 21829388 (PMID) GRASP2 eQTL
PROSTATE CANCER 5×10-16 23023329 (PMID) GWAS Catalog via SNiPA
Prostate cancer 5.3×10-16 23023329 (PMID) GRASP2 nonQTL
"Gene expression of LILRA3 [transcript NM_006865, probe A_23_P79094] in liver" 4.9×10-15 21637794 (PMID) GRASP2 eQTL
Gene expression of LILRA3 in blood cells in Celiac disease 1.4×10-13 19128478 (PMID) GRASP2 eQTL
Differential exon level expression of LILRB3 [probe 3870669] in peripheral blood mononuclear cells 4.9×10-12 19222302 (PMID) GRASP2 eQTL
Gene expression of LILRA3 [probe ILMN_1661631] in peripheral leukocytes 4.9×10-12 19966804 (PMID) GRASP2 eQTL
LILRA3 gene expression in human liver 9×10-12 20686565 (PMID) GRASP2 nonQTL
Triglycerides 2.3×10-11 24097068 (PMID) Supplemental file
Differential exon level expression of LILRB3 [probe 3870671] in peripheral blood mononuclear cells 4.6×10-11 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of LILRB3 [probe 3870663] in peripheral blood mononuclear cells 5.9×10-11 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of LILRB3 [probe 3870667] in peripheral blood mononuclear cells 1.1×10-10 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of LILRB3 [probe 3870670] in peripheral blood mononuclear cells 2.1×10-10 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of LILRB3 [probe 3870674] in peripheral blood mononuclear cells 4.8×10-10 19222302 (PMID) GRASP2 eQTL
Gene expression of LILRB3 [probe 3870611] in peripheral blood mononuclear cells 1.9×10-9 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of LILRB3 [probe 3870673] in peripheral blood mononuclear cells 6.3×10-9 19222302 (PMID) GRASP2 eQTL
Gene expression of LILRA3 (ENSG00000170866) in dendritic cells treated with Mycobacterium tuberculosis 7.7×10-9 22233810 (PMID) GRASP2 eQTL
Gene expression of TSEN34 in blood 9.7×10-9 21829388 (PMID) GRASP2 eQTL
cg02477834 (chr19:475551) 2.6×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Gene expression of LILRA3 [probeset 206881_s_at] in sputum 5.9×10-8 21949713 (PMID) GRASP2 eQTL
"Gene expression of LILRB3 [transcript NM_001081450, probe A_23_P368711] in liver" 9.3×10-8 21637794 (PMID) GRASP2 eQTL
Gene expression of LILRB5 in peripheral blood monocytes 6.4×10-7 20502693 (PMID) GRASP2 eQTL
Differential exon level expression of LILRB3 [probe 3870664] in peripheral blood mononuclear cells 2.5×10-6 19222302 (PMID) GRASP2 eQTL
Gene expression of LILRA3 in T cells 1.2×10-5 19644074 (PMID) GRASP2 eQTL
cg15441416 (chr19:54972071) 1.6×10-5 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Behcet's disease 2.2×10-5 23001997 (PMID) GRASP2 nonQTL
"Gene expression of LILRA4 [transcript NM_012276, probe A_23_P90497] in liver" 2.3×10-5 21637794 (PMID) GRASP2 eQTL
Advanced age-related macular degeneration (choroidal neovascularization) vs. no AMD 2.4×10-5 23455636 (PMID) GRASP2 nonQTL
Advanced age-related macular degeneration 6.6×10-5 23455636 (PMID) GRASP2 nonQTL
Total cholesterol 1.1×10-4 20686565 (PMID) GRASP2 nonQTL
Gene expression of LILRA3 (probeID ILMN_1661631) in breast tumors 1.7×10-4 22522925 (PMID) GRASP2 eQTL

Prostate cancer related.

This is a replicated cis-pQTL to Leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2). It is a risk-locus for prostate cancer [PubMed]. SNP rs103294 is in strong linkage equilibrium with a 6.7-kb germline deletion that removes the first six of seven exons in LILRA3 – reported in Chinese. Imputing yields much stronger associations, i.e. with coding variant rs386056.

The information gathered here is a result of an attempt to keep track of all interesting information that we encountered while investigating these loci. Please bear in mind that the annotation given here is neither complete nor free of errors, and that all information provided here should be confirmed by additional literature research before being used as a basis for firm conclusions or further experiments.