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

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Locus annotations

Locus 447

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
C4 cis Discovery rs1634718 6:30,972,865 A/G 0.25 996 -0.329 0.050 7.4×10-11 -1.060 3.8×10-10 1.4×10-10
C4 cis Replication rs1634718 6:30,972,865 A/G 0.17 337 -0.158 0.102 0.121 -1.020 0.415 0.125

 

Regional association plots

 

Boxplots and histograms for top associations

Complement C4 (C4)

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

Complement C4 (C4)

Target (abbrv.) C4
Target (full name) Complement C4
Somalogic ID (Sequence ID) SL000316 (4481-34_2)
Entrez Gene Symbol C4A, C4B
UniProt ID P0C0L4, P0C0L5
UniProt Comment
  • P0C0L4: Non-enzymatic component of C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. Covalently binds to immunoglobulins and immune complexes and enhances the solubilization of immune aggregates and the clearance of IC through CR1 on erythrocytes. C4A isotype is responsible for effective binding to form amide bonds with immune aggregates or protein antigens, while C4B isotype catalyzes the transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens.
  • P0C0L5: Non-enzymatic component of the C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. Covalently binds to immunoglobulins and immune complexes and enhances the solubilization of immune aggregates and the clearance of IC through CR1 on erythrocytes. C4A isotype is responsible for effective binding to form amide bonds with immune aggregates or protein antigens, while C4B isotype catalyzes the transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens.
Wiki Pathways
  • Complement Activation, Classical Pathway
  • SIDS Susceptibility Pathways
Reactome
  • Activation of C3 and C5
  • Initial triggering of complement
  • Regulation of Complement cascade

All locus annotations are based on the sentinel SNP (rs1634718) and 17 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
  • MUC21 mucin 21, cell surface associated
  • MUC22 mucin 22
Potentially regulated genes
eQTL genes
  • TRIM31 tripartite motif containing 31
  • CCHCR1 coiled-coil alpha-helical rod protein 1
  • HLA-C major histocompatibility complex, class I, C
  • MUC22 mucin 22
  • MICB MHC class I polypeptide-related sequence B
  • HCG22 HLA complex group 22
  • LINC00243
  • FLOT1 flotillin 1
  • C4A complement component 4A (Rodgers blood group)
  • VARS2 valyl-tRNA synthetase 2, mitochondrial
  • HCP5 HLA complex P5 (non-protein coding)
  • CYP21A1P cytochrome P450, family 21, subfamily A, polypeptide 1 pseudogene

 

Results from other genome-wide association studies

Trait P Study Source
Myasthenia gravis 3×10-68 23055271 (PMID) GRASP2 nonQTL
Idiopathic membranous nephropathy 2.5×10-25 21323541 (PMID) GRASP2 nonQTL
Gene expression of AL662797.7 in blood 4.1×10-23 21829388 (PMID) GRASP2 eQTL
Gene expression of VARSL in blood 3.9×10-18 21829388 (PMID) GRASP2 eQTL
Gene expression of BTN3A2 in peripheral blood monocytes 2×10-10 20502693 (PMID) GRASP2 eQTL
Gene expression of HCG27 in peripheral blood monocytes 7.6×10-10 20502693 (PMID) GRASP2 eQTL
Gene expression of HLA-DQA1 [probe 203290_at] in lymphoblastoid cell lines 4.8×10-9 17873877 (PMID) GRASP2 eQTL
Schizophrenia 2×10-8 25056061 (PMID) Supplemental file
Gene expression of VARS2 in peripheral blood monocytes 2.3×10-8 20502693 (PMID) GRASP2 eQTL
Lupus erythematosus, systemic 2.6×10-8 pha002867 (dbGaP) dbGaP via SNiPA
Gene expression of HLA-C [probe 216526_x_at] in lymphoblastoid cell lines 6.2×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of HLA-DRB1 [probe 221491_x_at] in lymphoblastoid cell lines 6.2×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of HLA-DRB2 [probe 221491_x_at] in lymphoblastoid cell lines 6.2×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of HLA-DRB3 [probe 221491_x_at] in lymphoblastoid cell lines 6.2×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of HLA-DRB4 [probe 221491_x_at] in lymphoblastoid cell lines 6.2×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of HLA-DRB5 [probe 221491_x_at] in lymphoblastoid cell lines 6.2×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of LOC100133484 [probe 221491_x_at] in lymphoblastoid cell lines 6.2×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of LOC100133661 [probe 221491_x_at] in lymphoblastoid cell lines 6.2×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of LOC100133811 [probe 221491_x_at] in lymphoblastoid cell lines 6.2×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of LOC730415 [probe 221491_x_at] in lymphoblastoid cell lines 6.2×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of LOC731718 [probe 221491_x_at] in lymphoblastoid cell lines 6.2×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of RNASE2 [probe 221491_x_at] in lymphoblastoid cell lines 6.2×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of ZNF749 [probe 221491_x_at] in lymphoblastoid cell lines 6.2×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of HLA-DRB1 [probe 204670_x_at] in lymphoblastoid cell lines 8.4×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of HLA-DRB2 [probe 204670_x_at] in lymphoblastoid cell lines 8.4×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of HLA-DRB3 [probe 204670_x_at] in lymphoblastoid cell lines 8.4×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of HLA-DRB4 [probe 204670_x_at] in lymphoblastoid cell lines 8.4×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of HLA-DRB5 [probe 204670_x_at] in lymphoblastoid cell lines 8.4×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of LOC100133484 [probe 204670_x_at] in lymphoblastoid cell lines 8.4×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of LOC100133661 [probe 204670_x_at] in lymphoblastoid cell lines 8.4×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of LOC100133811 [probe 204670_x_at] in lymphoblastoid cell lines 8.4×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of LOC730415 [probe 204670_x_at] in lymphoblastoid cell lines 8.4×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of RNASE2 [probe 204670_x_at] in lymphoblastoid cell lines 8.4×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of ZNF749 [probe 204670_x_at] in lymphoblastoid cell lines 8.4×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of HLA-C in peripheral blood monocytes 3.5×10-7 20502693 (PMID) GRASP2 eQTL
Gene expression of HLA-DQA1 in peripheral blood monocytes 3.1×10-6 20502693 (PMID) GRASP2 eQTL
Type 1 diabetes, Rheumatoid arthritis, combined case analysis 3×10-5 17554300 (PMID) GRASP2 nonQTL
Multiple sclerosis 1×10-4 19010793 (PMID) GRASP2 nonQTL
Waist circumfence, adjusted for BMI 1.4×10-4 25673412 (PMID) Supplemental file
Bipolar disorder vs. Schizophrenia 2×10-4 24280982 (PMID) Supplemental file
HbA1c 4.4×10-4 20858683 (PMID) Supplemental file
Gene expression of C6orf48 [probe 220755_s_at] in prefrontal cortex 4.7×10-4 20351726 (PMID) GRASP2 eQTL