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

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Locus annotations

Locus 205

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
MICA cis Discovery rs3828922 6:31,713,454 C/T 0.16 997 -0.532 0.058 2.3×10-19 -1.490 4.7×10-22 1.3×10-9
MICA cis Replication rs3828922 6:31,713,454 G/A 0.18 337 -0.270 0.092 0.004 -1.150 0.007 0.438
C34 gp41 HIV Fragment trans Discovery rs2075801 6:31,728,267 G/A 0.16 995 0.451 0.057 7.9×10-15 1.110 1.9×10-12 9.1×10-8
C34 gp41 HIV Fragment trans Replication rs2075801 6:31,728,267 G/A 0.19 337 0.285 0.081 5×10-4 1.090 0.003 0.038
C4 cis Discovery rs409558 6:31,708,147 T/C 0.16 996 0.386 0.059 1.2×10-10 1.070 1.7×10-9 4.5×10-10
C4 cis Replication rs2075788 6:31,712,181 A/C 0.19 337 0.069 0.099 0.486 1.010 0.753 0.521

 

Regional association plots

MHC class I polypeptide-related sequence A (MICA)

Download the association data used to generate this plot

gp41 C34 peptide, HIV (C34 gp41 HIV Fragment)

Download the association data used to generate this plot

Complement C4 (C4)

Download the association data used to generate this plot

 

Boxplots and histograms for top associations

MHC class I polypeptide-related sequence A (MICA)

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 C4 (C4)

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

MHC class I polypeptide-related sequence A (MICA)

Target (abbrv.) MICA
Target (full name) MHC class I polypeptide-related sequence A
Somalogic ID (Sequence ID) SL005199 (2730-58_2)
Entrez Gene Symbol MICA
UniProt ID Q29983
UniProt Comment
  • Seems to have no role in antigen presentation. Acts as a stress-induced self-antigen that is recognized by gamma delta T-cells. Ligand for the KLRK1/NKG2D receptor. Binding to KLRK1 leads to cell lysis.
Biomarker applications (based on IPA annotation)
  • safety
Pathway Studio
  • Natural Killer Cell Activation
  • Natural Killer Cell Activation through C-type Lectin-like Receptors

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.

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 (rs3828922) 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


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Genes hit or close-by
  • CLIC1 chloride intracellular channel 1
  • MSH5-SAPCD1 MSH5-SAPCD1 readthrough (NMD candidate)
  • MSH5 mutS homolog 5
  • SAPCD1-AS1 SAPCD1 antisense RNA 1
  • RNU6-850P RNA, U6 small nuclear 850, pseudogene
  • SAPCD1 suppressor APC domain containing 1
  • VARS valyl-tRNA synthetase
  • VWA7 von Willebrand factor A domain containing 7
eQTL genes
  • SKIV2L superkiller viralicidic activity 2-like (S. cerevisiae)
  • NELFE negative elongation factor complex member E
  • LY6G5C lymphocyte antigen 6 complex, locus G5C
  • AIF1 allograft inflammatory factor 1
  • HSPA1B heat shock 70kDa protein 1B
  • DXO decapping exoribonuclease
  • TNF tumor necrosis factor
  • LY6G6C lymphocyte antigen 6 complex, locus G6C
  • PRRC2A proline-rich coiled-coil 2A
  • C6orf48 chromosome 6 open reading frame 48
  • ATF6B activating transcription factor 6 beta
  • SNORD52 small nucleolar RNA, C/D box 52
  • BAG6 BCL2-associated athanogene 6

 

Results from other genome-wide association studies

Trait P Study Source
Gene expression of LY6G5C (probeID ILMN_1763467) in cerebellum in Alzheimer's disease cases and controls 5.6×10-16 22685416 (PMID) GRASP2 eQTL
Gene expression of MSH5 in peripheral blood monocytes 5.6×10-12 20502693 (PMID) GRASP2 eQTL
Gene expression of HLA-DQB1 in peripheral blood monocytes 2.6×10-10 20502693 (PMID) GRASP2 eQTL
Gene expression of HSPA1B in peripheral blood monocytes 2×10-9 20502693 (PMID) GRASP2 eQTL
Gene expression of HLA-DRB3 in peripheral blood monocytes 9.2×10-9 20502693 (PMID) GRASP2 eQTL
Advanced age-related macular degeneration 8.1×10-8 23455636 (PMID) GRASP2 nonQTL
Height 3.2×10-7 25282103 (PMID) Supplemental file
Advanced age-related macular degeneration (choroidal neovascularization) vs. no AMD 3.8×10-6 23455636 (PMID) GRASP2 nonQTL
Gene expression of LY6G5C (probeID ILMN_1763467) in temporal cortex in Alzheimer's disease cases and controls 4.6×10-6 22685416 (PMID) GRASP2 eQTL