HelmholtzZentrum munich
WCMC

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

ONLINE SUPPLEMENTARY INFORMATION

Home
Ideogram
Loci
Network view
Proteome annotation
Help
Locus annotations

Locus 137

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 rs2280774 6:31,928,691 G/A 0.37 993 -0.505 0.044 7.6×10-29 -1.240 1.8×10-28 2.4×10-24
C4b cis Replication rs2280774 6:31,928,691 G/A 0.26 337 -0.535 0.077 2.2×10-11 -1.270 6.9×10-10 7.1×10-5
C34 gp41 HIV Fragment trans Discovery rs2280774 6:31,928,691 G/A 0.37 993 -0.306 0.044 8.5×10-12 -1.080 2×10-10 5.3×10-7
C34 gp41 HIV Fragment trans Replication rs2280774 6:31,928,691 G/A 0.26 337 -0.252 0.070 3.5×10-4 -1.070 0.004 0.067

 

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

gp41 C34 peptide, HIV (C34 gp41 HIV Fragment)

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

gp41 C34 peptide, HIV (C34 gp41 HIV Fragment)

Target (abbrv.) C34 gp41 HIV Fragment
Target (full name) gp41 C34 peptide, HIV
Somalogic ID (Sequence ID) SL016148 (4792-51_2)
Entrez Gene Symbol Human-virus
UniProt ID Q70626
UniProt Comment
  • Envelope glycoprotein gp160: Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41.

All locus annotations are based on the sentinel SNP (rs2280774) and 18 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
  • C2 complement component 2
  • C2-AS1 C2 antisense RNA 1
  • XXbac-BPG116M5.17
  • NELFE negative elongation factor complex member E
  • CFB complement factor B
  • MIR1236 microRNA 1236
  • SKIV2L superkiller viralicidic activity 2-like (S. cerevisiae)
  • DXO decapping exoribonuclease
  • STK19 serine/threonine kinase 19
  • C4A complement component 4A (Rodgers blood group)
  • C4B complement component 4B (Chido blood group)
  • TNXB tenascin XB
  • CYP21A2 cytochrome P450, family 21, subfamily A, polypeptide 2
  • C4B-AS1 C4B antisense RNA 1
  • RNA5SP206 RNA, 5S ribosomal pseudogene 206
Potentially regulated genes
eQTL genes
  • HLA-DQB1 major histocompatibility complex, class II, DQ beta 1
  • PSORS1C3 psoriasis susceptibility 1 candidate 3 (non-protein coding)
  • HLA-DQB1-AS1 HLA-DQB1 antisense RNA 1
  • HLA-C major histocompatibility complex, class I, C
  • AIF1 allograft inflammatory factor 1
  • HSPA1B heat shock 70kDa protein 1B
  • MSH5 mutS homolog 5
  • BAG6 BCL2-associated athanogene 6
  • PRRC2A proline-rich coiled-coil 2A
  • HLA-B major histocompatibility complex, class I, B
  • VARS2 valyl-tRNA synthetase 2, mitochondrial
  • ATF6B activating transcription factor 6 beta
  • HSPA1L heat shock 70kDa protein 1-like
  • MSH5-SAPCD1 MSH5-SAPCD1 readthrough (NMD candidate)
  • DXO decapping exoribonuclease
  • XXbac-BPG300A18.13
  • XXbac-BPG248L24.12
  • CYP21A1P cytochrome P450, family 21, subfamily A, polypeptide 1 pseudogene
  • EHMT2 euchromatic histone-lysine N-methyltransferase 2
  • HLA-DQA2 major histocompatibility complex, class II, DQ alpha 2
  • CYP21A2 cytochrome P450, family 21, subfamily A, polypeptide 2
  • CCHCR1 coiled-coil alpha-helical rod protein 1
  • LST1 leukocyte specific transcript 1
  • NELFE negative elongation factor complex member E
  • NOTCH4 notch 4
  • AGPAT1 1-acylglycerol-3-phosphate O-acyltransferase 1
  • HLA-DRB5 major histocompatibility complex, class II, DR beta 5

 

Results from other genome-wide association studies

Trait P Study Source
Rheumatoid arthritis 3.4×10-106 20453842 (PMID) GRASP2 nonQTL
Rheumatoid arthritis (ACPA-positive) 1.2×10-34 21156761 (PMID) GRASP2 nonQTL
Serum Complement C4 3.5×10-24 23028341 (PMID) GRASP2 nonQTL
Complement C3 and C4 levels 1×10-22 23028341 (PMID) GWAS Catalog via SNiPA
Height 1.3×10-16 25282103 (PMID) Supplemental file
Gene expression of HSPA1B in blood 3×10-16 21829388 (PMID) GRASP2 eQTL
Gene expression of CYP21A2 (probeID ILMN_1773082) in temporal cortex in Alzheimer's disease cases and controls 3.5×10-14 22685416 (PMID) GRASP2 eQTL
Ulcerative colitis 5×10-14 24837172 (PMID) GWAS Catalog via SNiPA
cg12582959 (chr19:56159175) 3.4×10-13 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Advanced age-related macular degeneration 5.6×10-13 23455636 (PMID) GRASP2 nonQTL
cg14700577 (chr3:47516977) 3.3×10-11 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Gene expression of HLA-DQB1 [probe 209823_x_at] in lymphoblastoid cell lines 1.2×10-10 17873877 (PMID) GRASP2 eQTL
Advanced age-related macular degeneration (choroidal neovascularization) vs. no AMD 6.9×10-10 23455636 (PMID) GRASP2 nonQTL
Methylation levels at chr6:32184395-32184445 [hg18 coord, probe cg03543593] in Caudal pons 7.7×10-10 20485568 (PMID) GRASP2 meQTL
Gene expression of CYP21A2 (probeID ILMN_1773082) in cerebellum in Alzheimer's disease cases and controls 1.4×10-9 22685416 (PMID) GRASP2 eQTL
Systemic sclerosis 2.7×10-9 20383147 (PMID) GRASP2 nonQTL
Gene expression of HLA-DRB5 in peripheral blood monocytes 1.5×10-8 20502693 (PMID) GRASP2 eQTL
cg01255021 (chr16:1094629) 1.8×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg01620082 (chr3:125678431) 2.1×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Alopecia areata 3.2×10-8 20596022 (PMID) GRASP2 nonQTL
cg23656755 (chr1:230203067) 5.1×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Gene expression of HLA-DQB1 [probe 211656_x_at] in lymphoblastoid cell lines 5.3×10-8 17873877 (PMID) GRASP2 eQTL
cg06606381 (chr12:133084921) 6.6×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Gene expression of DDAH2 in peripheral blood monocytes 1×10-7 20502693 (PMID) GRASP2 eQTL
Schizophrenia 1.2×10-7 25056061 (PMID) Supplemental file
Gene expression of VARS2 in peripheral blood monocytes 6.5×10-7 20502693 (PMID) GRASP2 eQTL
Gene expression of NOTCH4 in peripheral blood monocytes 9.6×10-7 20502693 (PMID) GRASP2 eQTL
Gene expression of CSNK2B in peripheral blood monocytes 2×10-6 20502693 (PMID) GRASP2 eQTL
Crohn's disease 3.3×10-6 Supplemental file
Gene expression of HLA-DRB4 in peripheral blood monocytes 6×10-6 20502693 (PMID) GRASP2 eQTL
Gene expression of RNF5///AGER in blood 8.6×10-6 21829388 (PMID) GRASP2 eQTL
Pemphigus vulgaris 1×10-5 22437316 (PMID) GRASP2 nonQTL
Inflammatory bowel disease 2×10-5 Supplemental file
Alcohol behavior (binary alcohol dependence diagnosis) 3.4×10-5 21529783 (PMID) GRASP2 nonQTL
Sarcoidosis 3.4×10-5 22952805 (PMID) GRASP2 nonQTL
Gene expression of C6orf48///SNORD52 in blood 4.2×10-5 21829388 (PMID) GRASP2 eQTL
Adult asthma 1.6×10-4 21804548 (PMID) GRASP2 nonQTL
Waist-to-hip ratio, adjusted for BMI 2.2×10-4 25673412 (PMID) Supplemental file
Fasting insulin, adjusted for BMI 2.6×10-4 22885924 (PMID) Supplemental file
Bipolar disorder vs. Schizophrenia 4.7×10-4 24280982 (PMID) Supplemental file
Late onset Alzheimer's disease 4.7×10-4 21390209 (PMID) GRASP2 nonQTL
Coronary artery calcification (CAC) 4.9×10-4 23727086 (PMID) GRASP2 nonQTL