HelmholtzZentrum munich
WCMC

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

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 387

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
granzyme A trans Discovery rs2853928 6:31,257,511 C/A 0.23 994 -0.363 0.051 3.4×10-12 -1.080 2×10-10 2.1×10-6
granzyme A trans Replication rs2853928 6:31,257,511 C/A 0.11 337 -0.230 0.093 0.014 -1.080 0.016 0.036

 

Regional association plots

 

Boxplots and histograms for top associations

Granzyme A (granzyme A)

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

Granzyme A (granzyme A)

Target (abbrv.) granzyme A
Target (full name) Granzyme A
Somalogic ID (Sequence ID) SL004298 (3440-7_2)
Entrez Gene Symbol GZMA
UniProt ID P12544
UniProt Comment
  • Abundant protease in the cytosolic granules of cytotoxic T-cells and NK-cells which activates caspase-independent cell death with morphological features of apoptosis when delivered into the target cell through the immunological synapse. It cleaves after Lys or Arg. Cleaves APEX1 after 'Lys-31' and destroys its oxidative repair activity. Cleaves the nucleosome assembly protein SET after 'Lys-189', which disrupts its nucleosome assembly activity and allows the SET complex to translocate into the nucleus to nick and degrade the DNA.
Pathway Interaction Database
  • IL12-mediated signaling events
Pathway Studio
  • CD8+ T-cell Activation
  • Cell Death Mediated by Cytotoxic Cells
  • Natural Killer Cell Activation

All locus annotations are based on the sentinel SNP (rs2853928) and 16 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
eQTL genes
  • PSORS1C3 psoriasis susceptibility 1 candidate 3 (non-protein coding)
  • HLA-C major histocompatibility complex, class I, C
  • XXbac-BPG299F13.17
  • TCF19 transcription factor 19
  • HLA-B major histocompatibility complex, class I, B
  • VARS2 valyl-tRNA synthetase 2, mitochondrial
  • HCG27 HLA complex group 27 (non-protein coding)
  • PSORS1C2 psoriasis susceptibility 1 candidate 2
  • XXbac-BPG181B23.7
  • XXbac-BPG248L24.12
  • CCHCR1 coiled-coil alpha-helical rod protein 1
  • WASF5P WAS protein family, member 5, pseudogene
  • CYP21A1P cytochrome P450, family 21, subfamily A, polypeptide 1 pseudogene
  • DDX39B DEAD (Asp-Glu-Ala-Asp) box polypeptide 39B
  • PSORS1C1 psoriasis susceptibility 1 candidate 1
  • LINC00243
  • ATP6V1G2 ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2
  • XXbac-BPG248L24.13
  • MICA MHC class I polypeptide-related sequence A
  • MICB MHC class I polypeptide-related sequence B
  • TSSC4 tumor suppressing subtransferable candidate 4
  • TMEM154 transmembrane protein 154
  • FLOT1 flotillin 1
  • XRCC6 X-ray repair complementing defective repair in Chinese hamster cells 6
  • CD248 CD248 molecule, endosialin
  • CSF3R colony stimulating factor 3 receptor (granulocyte)
  • HCG22 HLA complex group 22
  • BAG6 BCL2-associated athanogene 6
  • C4B complement component 4B (Chido blood group)
  • TNXB tenascin XB

 

Results from other genome-wide association studies

Trait P Study Source
cg23656755 (chr1:230203067) 1.2×10-128 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg01620082 (chr3:125678431) 3.2×10-81 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg06606381 (chr12:133084921) 1.8×10-76 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg17862947 (chr12:133086950) 2.6×10-74 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Gene expression of HLA-C (probeID ILMN_2150787) in cerebellum in Alzheimer's disease cases and controls 4.8×10-60 22685416 (PMID) GRASP2 eQTL
Gene expression of HLA-C (probeID ILMN_2150787) in temporal cortex in Alzheimer's disease cases and controls 5.8×10-56 22685416 (PMID) GRASP2 eQTL
Gene expression of HLA-G in liver 1.3×10-44 18462017 (PMID) GRASP2 eQTL
Height 8.3×10-35 25282103 (PMID) Supplemental file
Gene expression of HLA-C (probeID ILMN_2150787) in cerebellum in non-Alzheimer's disease samples 3.8×10-30 22685416 (PMID) GRASP2 eQTL
Gene expression of HLA-C (probeID ILMN_2150787) in cerebellum in Alzheimer's disease cases 5.5×10-29 22685416 (PMID) GRASP2 eQTL
CD4:CD8 lymphocyte ratio 2×10-28 20045101 (PMID) GWAS Catalog via SNiPA
Lymphocyte levels (CD4:CD8) 2.1×10-28 20045101 (PMID) GRASP2 nonQTL
Gene expression of HLA-C (probeID ILMN_2150787) in temporal cortex in Alzheimer's disease cases 3×10-28 22685416 (PMID) GRASP2 eQTL
Gene expression of HLA-C (probeID ILMN_2150787) in temporal cortex in non-Alzheimer's disease samples 3.7×10-27 22685416 (PMID) GRASP2 eQTL
cg10154826 (chr6:17601018) 2.2×10-25 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Gene expression of TMEM154 in blood 1.8×10-24 21829388 (PMID) GRASP2 eQTL
Gene expression of HCG27 in blood 1.5×10-23 21829388 (PMID) GRASP2 eQTL
Total cholesterol 3.9×10-21 24097068 (PMID) Supplemental file
Lymphocyte levels (CD8) 6.2×10-21 20045101 (PMID) GRASP2 nonQTL
Differential exon level expression of HLA-C [probe 2948901] in brain cortex 1.2×10-20 19222302 (PMID) GRASP2 eQTL
cg02753903 (chr19:38943549) 2.2×10-20 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Triglycerides 2.2×10-20 24097068 (PMID) Supplemental file
Gene expression of HLA-C [probe 2948887] in brain cortex 3.9×10-19 19222302 (PMID) GRASP2 eQTL
Gene expression of XRCC6 in blood 2.5×10-18 21829388 (PMID) GRASP2 eQTL
cg07408552 (chr17:40612019) 3×10-18 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg17841099 (chr1:153940066) 7.5×10-18 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg17169043 (chr6:170863821) 1.7×10-17 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Differential exon level expression of HLA-C [probe 2948904] in peripheral blood mononuclear cells 9×10-16 19222302 (PMID) GRASP2 eQTL
cg07408989 (chr17:7116768) 1.3×10-15 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Differential exon level expression of HLA-C [probe 2948901] in peripheral blood mononuclear cells 6×10-15 19222302 (PMID) GRASP2 eQTL
cg06419846 (chr11:66083721) 2.5×10-14 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Differential exon level expression of HLA-C [probe 2948915] in peripheral blood mononuclear cells 7.4×10-14 19222302 (PMID) GRASP2 eQTL
Idiopathic membranous nephropathy 9.1×10-14 21323541 (PMID) GRASP2 nonQTL
cg01255021 (chr16:1094629) 1.4×10-13 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Gene expression of hmm31752 in CEU-CHB-JPT-YRI lymphoblastoid cell lines 1.6×10-13 17873874 (PMID) GRASP2 eQTL
Differential exon level expression of HLA-C [probe 2948915] in brain cortex 2.4×10-13 19222302 (PMID) GRASP2 eQTL
cg05496363 (chr11:66083790) 3.1×10-13 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Differential exon level expression of [probeset 2902222] in peripheral blood mononuclear cells 1×10-12 19222302 (PMID) GRASP2 eQTL
HIV-1 control 1.2×10-12 21051598 (PMID) GRASP2 nonQTL
cg10213762 (chr6:169284343) 1.4×10-12 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Differential exon level expression of HLA-C [probe 2948918] in peripheral blood mononuclear cells 1.5×10-12 19222302 (PMID) GRASP2 eQTL
CCHCR1 gene expression 1.9×10-12 20045101 (PMID) GRASP2 nonQTL
Gene expression of CCHCR1 [probe 209698_at] in lymphoblastoid cell lines 1.9×10-12 17873877 (PMID) GRASP2 eQTL
Height tails (upper and lower 5th percentiles) 3.6×10-12 23563607 (PMID) GRASP2 nonQTL
cg22213242 (chr11:66083549) 6.6×10-12 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg03984502 (chr1:151805637) 7.2×10-12 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Differential exon level expression of HLA-C [probe 2948897] in peripheral blood mononuclear cells 1.1×10-11 19222302 (PMID) GRASP2 eQTL
Gene expression of HLA-C in CEU-CHB-JPT-YRI lymphoblastoid cell lines 1.9×10-11 17873874 (PMID) GRASP2 eQTL
cg17329534 (chr1:154980719) 3.7×10-11 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
HIV-1 control (viral load at set point) 4.4×10-11 20041166 (PMID) GRASP2 nonQTL
cg22379212 (chr19:38944024) 4.4×10-11 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Schizophrenia 4.4×10-11 25056061 (PMID) Supplemental file
cg18224038 (chr2:87042695) 8.5×10-11 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg21578195 (chr20:62168703) 9×10-11 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Immune control of HIV-1 viremia 9.1×10-11 20045101 (PMID) GRASP2 nonQTL
cg25652859 (chr20:57427388) 1×10-10 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg03407631 (chr6:52998845) 1.1×10-10 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Gene expression of HLA-C [probe 2948887] in peripheral blood mononuclear cells 1.2×10-10 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of HLA-B [probe 2948952] in peripheral blood mononuclear cells 1.2×10-10 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of HLA-C [probe 2948907] in peripheral blood mononuclear cells 1.5×10-10 19222302 (PMID) GRASP2 eQTL
cg19589727 (chr20:57427786) 1.6×10-10 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg15128876 (chr1:161146049) 1.8×10-10 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
HLA-B gene expression in HIV-infected CD4+ T cells 2×10-10 20195503 (PMID) GRASP2 eQTL
cg11067179 (chr11:66083565) 2.4×10-10 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg12550496 (chr6:169284320) 2.5×10-10 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg15007120 (chr3:109128526) 3.2×10-10 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg24137511 (chr19:18260306) 3.3×10-10 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Methylation levels at chr6:31347249-31347299 [hg18 coord, probe cg10409680] in Temporal cortex 4×10-10 20485568 (PMID) GRASP2 meQTL
cg06065549 (chr20:57427419) 4.4×10-10 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Lupus erythematosus, systemic 5.2×10-10 pha002848 (dbGaP) dbGaP via SNiPA
Differential exon level expression of [probeset 2902222] in brain cortex 5.4×10-10 19222302 (PMID) GRASP2 eQTL
cg08127462 (chr1:153514240) 8.2×10-10 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg19473529 (chr20:48726807) 1.2×10-9 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Gene expression of HLA-C in Lymphoblastoid cell lines 1.3×10-9 19644074 (PMID) GRASP2 eQTL
Type 1 diabetes 1.8×10-9 17632545 (PMID) GRASP2 nonQTL
cg01949403 (chr22:36562378) 2.3×10-9 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg06099246 (chr16:1094837) 2.4×10-9 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg14564778 (chr20:57427532) 2.5×10-9 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
HLA-B gene expression 2.5×10-9 20045101 (PMID) GRASP2 nonQTL
cg19808620 (chr1:153514466) 3.1×10-9 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Gene expression of HLA-C [probe ILMN_23822] in osteoblasts 3.5×10-9 19654370 (PMID) GRASP2 eQTL
Methylation levels at chr6:31347249-31347299 [hg18 coord, probe cg10409680] in Frontal cortex 3.6×10-9 20485568 (PMID) GRASP2 meQTL
Methylation levels at chr6:31538845-31538895 [hg18 coord, probe cg13784557] in Temporal cortex 7.3×10-9 20485568 (PMID) GRASP2 meQTL
cg06706159 (chr19:18260326) 7.9×10-9 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg25598890 (chr12:117501471) 1×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg13210595 (chr1:167471288) 1×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg12321149 (chr20:57427402) 1.1×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
LDL cholesterol 1.4×10-8 24097068 (PMID) Supplemental file
cg27661264 (chr20:57427762) 1.8×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Methylation levels at chr6:31954925-31954975 [hg18 coord, probe cg07363637] in Temporal cortex 2×10-8 20485568 (PMID) GRASP2 meQTL
cg00236729 (chr10:62409841) 2×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg17372758 (chr10:73976774) 2.5×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg22354132 (chr1:55273613) 3.1×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg17414107 (chr20:57427854) 3.3×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg19640589 (chr20:57427997) 3.5×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg04232128 (chr5:138861217) 3.7×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg22787191 (chr1:245524793) 3.8×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg20528838 (chr20:57427754) 3.9×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
HLA-C gene expression 4.4×10-8 17641165 (PMID) GRASP2 nonQTL
cg02042585 (chr6:160783761) 5.4×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg17768600 (chr6:160783969) 6.7×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg18651192 (chr3:125677598) 7.4×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Differential exon level expression of HLA-C [probe 2948914] in brain cortex 7.9×10-8 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of HLA-C [probe 2948904] in brain cortex 8.5×10-8 19222302 (PMID) GRASP2 eQTL
Gene expression of MICA in normal prepouch ileum 9.3×10-8 23474282 (PMID) GRASP2 eQTL
cg01817393 (chr20:57427618) 10×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg02976539 (chr17:72757278) 1.1×10-7 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg22900360 (chr10:72360348) 1.5×10-7 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg17051543 (chr10:135092265) 1.6×10-7 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Hip circumfence, adjusted for BMI 1.7×10-7 25673412 (PMID) Supplemental file
cg04257105 (chr20:57427689) 1.8×10-7 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg11011533 (chr17:3674625) 1.9×10-7 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg00262061 (chr3:39322751) 2×10-7 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg07105596 (chr20:57427496) 2×10-7 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Differential exon level expression of HLA-B [probe 2948958] in peripheral blood mononuclear cells 2.1×10-7 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of HLA-C [probe 2948906] in brain cortex 2.5×10-7 19222302 (PMID) GRASP2 eQTL
cg02135077 (chr8:103820794) 2.5×10-7 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg10302550 (chr20:57427845) 2.5×10-7 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Differential exon level expression of HLA-B [probe 2948946] in peripheral blood mononuclear cells 3×10-7 19222302 (PMID) GRASP2 eQTL
Rheumatoid arthritis 3×10-7 17804836 (PMID) GRASP2 nonQTL
Gene expression of hmm31752 in CHB-JPT lymphoblastoid cell lines 3.2×10-7 17873874 (PMID) GRASP2 eQTL
Gene expression of HCG27 (probeID ILMN_1746436) in temporal cortex in Alzheimer's disease cases and controls 3.2×10-7 22685416 (PMID) GRASP2 eQTL
Waist-to-hip ratio, adjusted for BMI 3.3×10-7 25673412 (PMID) Supplemental file
Sarcoidosis 4.5×10-7 22952805 (PMID) GRASP2 nonQTL
Gene expression of HLA-B [probeset 211911_x_at] in sputum 6.3×10-7 21949713 (PMID) GRASP2 eQTL
Differential exon level expression of HLA-C [probe 2948893] in peripheral blood mononuclear cells 7.3×10-7 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of HLA-C [probe 2948909] in peripheral blood mononuclear cells 1.2×10-6 19222302 (PMID) GRASP2 eQTL
Crohn's disease 1.3×10-6 Supplemental file
Bipolar disorder vs. Schizophrenia 2.5×10-6 24280982 (PMID) Supplemental file
HIV-1 seropositive nonprogression 2.9×10-6 19115949 (PMID) GRASP2 nonQTL
Hip circumfence 3×10-6 25673412 (PMID) Supplemental file
Gene expression of HCG27 (probeID ILMN_1746436) in cerebellum in Alzheimer's disease cases and controls 7.2×10-6 22685416 (PMID) GRASP2 eQTL
Differential exon level expression of HLA-C [probe 2948893] in brain cortex 7.4×10-6 19222302 (PMID) GRASP2 eQTL
Lung cancer 7.8×10-6 19836008 (PMID) GRASP2 nonQTL
HIV-1 control (viral load) 8.6×10-6 21490045 (PMID) GRASP2 nonQTL
Gene expression of ATP6V1G2///BAT1 in blood 9.9×10-6 21829388 (PMID) GRASP2 eQTL
Differential exon level expression of HLA-C [probe 2948918] in brain cortex 2.1×10-5 19222302 (PMID) GRASP2 eQTL
Multiple sclerosis 2.8×10-5 20598377 (PMID) GRASP2 nonQTL
Irritible bowel syndrome 3×10-5 18587394 (PMID) GRASP2 nonQTL
Differential exon level expression of HLA-C [probe 2948897] in brain cortex 3.8×10-5 19222302 (PMID) GRASP2 eQTL
Gene expression of HLA-C [probeset 214459_x_at] in sputum 4×10-5 21949713 (PMID) GRASP2 eQTL
Blood pressure 7.1×10-5 pha003050 (dbGaP) dbGaP via SNiPA
Gene expression of HCG27 (probeID ILMN_1746436) in cerebellum in Alzheimer's disease cases 9.7×10-5 22685416 (PMID) GRASP2 eQTL
Gene expression of HLA-C [probeset 208812_x_at] in sputum 1.3×10-4 21949713 (PMID) GRASP2 eQTL
Differential exon level expression of HLA-C [probeset 2948907] in brain cortex 2.1×10-4 19222302 (PMID) GRASP2 eQTL
Differential exon level expression of HLA-C [probeset 2948897] in brain cortex 2.3×10-4 19222302 (PMID) GRASP2 eQTL
Waist-to-hip ratio 3.3×10-4 25673412 (PMID) Supplemental file