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

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Locus annotations

Locus 379

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
C4b cis Discovery rs204888 6:32,089,142 G/T 0.10 997 0.528 0.074 2.5×10-12 1.260 3.1×10-12 4.2×10-13
C4b cis Replication rs204899 6:32,057,627 G/A 0.23 337 0.340 0.087 1.1×10-4 1.150 0.001 0.187

 

Regional association plots

 

Boxplots and histograms for top associations

Complement C4b (C4b)

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

Complement C4b (C4b)

Target (abbrv.) C4b
Target (full name) Complement C4b
Somalogic ID (Sequence ID) SL000318 (2182-54_1)
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 (rs204888) 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
  • TNXB tenascin XB
  • ATF6B activating transcription factor 6 beta
  • FKBPL FK506 binding protein like
Potentially regulated genes
eQTL genes
  • SKIV2L superkiller viralicidic activity 2-like (S. cerevisiae)
  • TNXA tenascin XA (pseudogene)
  • LST1 leukocyte specific transcript 1
  • EHMT2 euchromatic histone-lysine N-methyltransferase 2
  • ABCF1 ATP-binding cassette, sub-family F (GCN20), member 1

 

Results from other genome-wide association studies

Trait P Study Source
Rheumatoid arthritis 9×10-24 20453842 (PMID) GRASP2 nonQTL
Advanced age-related macular degeneration 3.9×10-11 23455636 (PMID) GRASP2 nonQTL
Rheumatoid arthritis (ACPA-positive) 1×10-10 21156761 (PMID) GRASP2 nonQTL
Advanced age-related macular degeneration (choroidal neovascularization) vs. no AMD 5.1×10-9 23455636 (PMID) GRASP2 nonQTL
Crohn's disease 6.7×10-5 Supplemental file
Advanced age-related macular degeneration (geographic atrophy) 3.7×10-4 23455636 (PMID) GRASP2 nonQTL