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

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Locus annotations

Locus 16

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
FCG2A/B cis Discovery rs7551957 1:161,470,042 T/C 0.43 992 0.886 0.035 2.2×10-111 1.730 1.1×10-111 4.8×10-82
FCG2A/B cis Replication rs1801274 1:161,479,745 A/G 0.41 337 0.872 0.059 8.5×10-38 1.600 5.5×10-32 6.9×10-21

 

Regional association plots

Low affinity immunoglobulin gamma Fc region receptor II-a/b (FCG2A/B)

Download the association data used to generate this plot

 

Boxplots and histograms for top associations

Low affinity immunoglobulin gamma Fc region receptor II-a/b (FCG2A/B)

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

Low affinity immunoglobulin gamma Fc region receptor II-a/b (FCG2A/B)

Target (abbrv.) FCG2A/B
Target (full name) Low affinity immunoglobulin gamma Fc region receptor II-a/b
Somalogic ID (Sequence ID) SL017613 (3310-62_1)
Entrez Gene Symbol FCGR2A
UniProt ID P12318, P31994
UniProt Comment
  • P12318: Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens. Promotes phagocytosis of opsonized antigens.
  • P31994: Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B-cells. Binding to this receptor results in down-modulation of previous state of cell activation triggered via antigen receptors on B-cells (BCR), T-cells (TCR) or via another Fc receptor. Isoform IIB1 fails to mediate endocytosis or phagocytosis. Isoform IIB2 does not trigger phagocytosis.
Pathway Interaction Database
  • BCR signaling pathway
  • Fc-epsilon receptor I signaling in mast cells
Reactome
  • Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Pathway Studio
  • T-cell-Independent B-cell Activation

All locus annotations are based on the sentinel SNP (rs7551957) and 5 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
  • FCGR2A Fc fragment of IgG, low affinity IIa, receptor (CD32)
eQTL genes
  • SDHC succinate dehydrogenase complex, subunit C, integral membrane protein, 15kDa

 

Results from other genome-wide association studies

Trait P Study Source
Inflammatory bowel disease 2×10-38 23128233 (PMID) GWAS Catalog via SNiPA
Ulcerative colitis 2×10-20 21297633 (PMID) GWAS Catalog via SNiPA
Ulcerative collitis 3.8×10-17 Supplemental file
P12318 protein abundance levels 5.2×10-15 22595970 (PMID) GRASP2 pQTL
Kawasaki disease 7×10-11 22081228 (PMID) GWAS Catalog via SNiPA
Gene expression of FCGR2B in blood 9.5×10-9 21829388 (PMID) GRASP2 eQTL
Total cholesterol 3.7×10-8 23063622 (PMID) GRASP2 nonQTL
Differential exon level expression of FCGR2A [probe 2363750] in peripheral blood mononuclear cells 1.2×10-7 19222302 (PMID) GRASP2 eQTL
cg07890827 (chr10:131636646) 2×10-7 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Total colectomy in ulcerative colitis 2.3×10-7 19915573 (PMID) GRASP2 nonQTL
Systemic lupus erythematosus (SLE) (females) 6.8×10-7 18204446 (PMID) GRASP2 nonQTL
Triglycerides 1.5×10-6 24097068 (PMID) Supplemental file
Ulcerative colitis (Smoking) 4.6×10-6 19915573 (PMID) GRASP2 nonQTL
SYSTEMIC LUPUS ERYTHEMATOSUS 9×10-6 24871463 (PMID) GWAS Catalog via SNiPA
LDL cholesterol 1.9×10-5 24097068 (PMID) Supplemental file
Ulcerative colitis age of onset <30 2.9×10-5 19915573 (PMID) GRASP2 nonQTL
Systemic lupus erythematosus (SLE) 4.7×10-5 21408207 (PMID) GRASP2 nonQTL
Rheumatoid arthritis 5.1×10-5 20453842 (PMID) GRASP2 nonQTL
PCP4L1 gene expression in subcutaneous adipose tissue 6.7×10-5 21602305 (PMID) GRASP2 eQTL
Ulcerative colitis age of onset >=30 1×10-4 19915573 (PMID) GRASP2 nonQTL
Pan ulcerative colitis 1×10-4 19915573 (PMID) GRASP2 nonQTL
Gene expression of FCGR2A in blood 2.4×10-4 21829388 (PMID) GRASP2 eQTL
Schizophrenia 4.3×10-4 25056061 (PMID) Supplemental file

FCGR2B protein levels may influence the risk to develop auto-immune disorders.

Two replicated cis-pQTLs with Low affinity immunoglobulin gamma Fc region receptor II-b (FCGR2B). rs7551957 is a strong GWAS hit for Inflammatory bowel disease (p<2×10-38) and related auto-immune diseases (Ulcerative colitis, Kawasaki disease, systemic lupus erythematous, Inflammatory bowel disease). This association can shed new light on the functional background of the role of FCGR2B in Chrohn's disease. See also Locus 141 for an association with the ratio of FCGR2B and FCGR3B.

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.