HelmholtzZentrum munich
WCMC

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

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 142

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
Factor B cis Discovery rs4151669 6:31,915,144 G/A 0.04 997 -1.170 0.104 6.3×10-28 -1.170 1.3×10-29 3×10-26

 

Regional association plots

 

Boxplots and histograms for top associations

Complement factor B (Factor B)

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

Complement factor B (Factor B)

Target (abbrv.) Factor B
Target (full name) Complement factor B
Somalogic ID (Sequence ID) SL000414 (4129-72_1)
Entrez Gene Symbol CFB
UniProt ID P00751
UniProt Comment
  • Factor B which is part of the alternate pathway of the complement system is cleaved by factor D into 2 fragments: Ba and Bb. Bb, a serine protease, then combines with complement factor 3b to generate the C3 or C5 convertase. It has also been implicated in proliferation and differentiation of preactivated B-lymphocytes, rapid spreading of peripheral blood monocytes, stimulation of lymphocyte blastogenesis and lysis of erythrocytes. Ba inhibits the proliferation of preactivated B-lymphocytes.
Reactome
  • Activation of C3 and C5
  • Alternative complement activation
  • Regulation of Complement cascade
Pathway Studio
  • Alternative Complement Pathway

All locus annotations are based on the sentinel SNP (rs4151669) and 21 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.

Linked genes

Genes hit or close-by
  • EHMT2 euchromatic histone-lysine N-methyltransferase 2
  • SLC44A4 solute carrier family 44, member 4
  • EHMT2-AS1 EHMT2 antisense RNA 1
  • ZBTB12 zinc finger and BTB domain containing 12
  • C2 complement component 2
  • XXbac-BPG116M5.17
  • C2-AS1 C2 antisense RNA 1
  • CFB complement factor B
  • NELFE negative elongation factor complex member E
  • MIR1236 microRNA 1236
  • DXO decapping exoribonuclease
  • STK19 serine/threonine kinase 19
  • C4A complement component 4A (Rodgers blood group)
eQTL genes
  • DXO decapping exoribonuclease
  • C6orf48 chromosome 6 open reading frame 48
  • XXbac-BPG246D15.9
  • HLA-DOB major histocompatibility complex, class II, DO beta
  • HLA-B major histocompatibility complex, class I, B

 

Results from other genome-wide association studies

Trait P Study Source
Age-related macular degeneration 2×10-23 21665990 (PMID) GWAS Catalog via SNiPA
Advanced age-related macular degeneration 2.4×10-23 21665990 (PMID) GRASP2 nonQTL
Gene expression of FFAR2 in liver 3.5×10-20 18462017 (PMID) GRASP2 eQTL
Gene expression of HSS00126305 in liver 4.8×10-16 18462017 (PMID) GRASP2 eQTL
Rheumatoid arthritis 6.3×10-15 22446960 (PMID) Supplemental file
Advanced age-related macular degeneration (choroidal neovascularization) vs. no AMD 4.7×10-13 23455636 (PMID) GRASP2 nonQTL
Serum myeloperoxidase levels 4.8×10-10 23620142 (PMID) GRASP2 nonQTL
Macular degeneration 6.1×10-10 pha002869 (dbGaP) dbGaP via SNiPA
Gene expression of DOM3Z (probeID ILMN_1726990) in cerebellum in Alzheimer's disease cases and controls 6.3×10-9 22685416 (PMID) GRASP2 eQTL
Age-related macular degeneration (CNV) 2×10-8 22705344 (PMID) GWAS Catalog via SNiPA
Gene expression of DOM3Z (probeID ILMN_1726990) in temporal cortex in Alzheimer's disease cases and controls 5.3×10-8 22685416 (PMID) GRASP2 eQTL
Advanced age-related macular degeneration (geographic atrophy) 1.7×10-7 23455636 (PMID) GRASP2 nonQTL
Age-related macular degeneration (GA) 1×10-6 22705344 (PMID) GWAS Catalog via SNiPA
Gene expression of DOM3Z (probeID ILMN_1726990) in cerebellum in non-Alzheimer's disease samples 3.6×10-6 22685416 (PMID) GRASP2 eQTL
Gene expression of CREBL1 [probe ILMN_21310] in osteoblasts treated with PGE2 4.7×10-5 21283786 (PMID) GRASP2 eQTL
Exudative age-related macular degeneration 2×10-4 21909106 (PMID) GRASP2 nonQTL
Total cholesterol 2.2×10-4 24097068 (PMID) Supplemental file