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

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Locus annotations

Locus 416

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
Caspase-3 cis Discovery rs870825 4:185,588,045 A/G 0.16 995 -0.396 0.058 1.8×10-11 -1.140 3.1×10-10 8.4×10-6
Caspase-3 cis Replication rs72689273 4:185,592,750 G/A 0.14 337 -0.152 0.062 0.014 -1.130 0.022 0.026

 

Regional association plots

 

Boxplots and histograms for top associations

Caspase-3

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

Caspase-3

Target (abbrv.) Caspase-3
Target (full name) Caspase-3
Somalogic ID (Sequence ID) SL003711 (3593-72_3)
Entrez Gene Symbol CASP3
UniProt ID P42574
UniProt Comment
  • Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis it proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Involved in the cleavage of huntingtin. Triggers cell adhesion in sympathetic neurons through RET cleavage.
Targeted by drugs (based on IPA annotation)
  • emricasan
Biomarker applications (based on IPA annotation)
  • diagnosis
  • disease progression
  • efficacy
  • unspecified application
Wiki Pathways
  • Alzheimers Disease
  • Apoptosis
  • Apoptosis Modulation and Signaling
  • Apoptosis Modulation by HSP70
  • DNA damage response
  • FAS pathway and Stress induction of HSP regulation
  • Integrated Breast Cancer Pathway
  • Integrated Cancer pathway
  • MAPK signaling pathway
  • Prolactin Signaling Pathway
  • TNF alpha Signaling Pathway
  • TWEAK Signaling Pathway
  • miRNA regulation of DNA Damage Response
Pathway Interaction Database
  • Calcineurin-regulated NFAT-dependent transcription in lymphocytes
  • Caspase Cascade in Apoptosis
  • FAS (CD95) signaling pathway
  • HIV-1 Nef: Negative effector of Fas and TNF-alpha
  • LPA receptor mediated events
  • Posttranslational regulation of adherens junction stability and dissassembly
  • Role of Calcineurin-dependent NFAT signaling in lymphocytes
  • Syndecan-2-mediated signaling events
  • p75(NTR)-mediated signaling
Reactome
  • Activation of DNA fragmentation factor
  • Activation of caspases through apoptosome-mediated cleavage
  • Apoptotic cleavage of cell adhesion proteins
  • Apoptotic cleavage of cellular proteins
  • Caspase-mediated cleavage of cytoskeletal proteins
  • Degradation of the extracellular matrix
  • Ligand-independent caspase activation via DCC
  • NADE modulates death signalling
  • SMAC binds to IAPs
  • SMAC-mediated dissociation of IAP:caspase complexes
  • Signaling by Hippo
  • Stimulation of the cell death response by PAK-2p34
Pathway Studio
  • Apoptosis
  • Cell Death Mediated by Cytotoxic Cells
  • Cleavage of Lamina in Apoptosis
  • Natural Killer Cell Activation through C-type Lectin-like Receptors
  • Natural Killer Cell Activation through ITAM-Containing Receptors
  • Natural Killer Cell Activation through ITSM-Containing Receptors
  • Peripheral T-cell Tolerance Overview
  • TNFRSF6 → FOXO3A signaling

All locus annotations are based on the sentinel SNP (rs870825) and 88 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
  • PRIMPOL primase and polymerase (DNA-directed)
  • CASP3 caspase 3, apoptosis-related cysteine peptidase
Potentially regulated genes
eQTL genes
  • PRIMPOL primase and polymerase (DNA-directed)
  • CASP3 caspase 3, apoptosis-related cysteine peptidase
  • CENPU centromere protein U

 

Results from other genome-wide association studies

Trait P Study Source
Gene expression of CASP3 in blood 1.5×10-12 21829388 (PMID) GRASP2 eQTL
cg22905866 (chr4:185468801) 4.8×10-9 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
PC aa C40:2 / PC aa C40:5 6.5×10-7 20037589 (PMID) GRASP2 metabQTL
Gene expression of LRRC6 in peripheral blood monocytes 7.4×10-6 20502693 (PMID) GRASP2 eQTL
Gene expression of ISLR2 in peripheral blood monocytes 7.7×10-6 20502693 (PMID) GRASP2 eQTL
Serum ratio of (cysteine)/(N-acetylthreonine) 3.5×10-5 21886157 (PMID) GRASP2 metabQTL
Serum concentration of erythrose 1.8×10-4 21886157 (PMID) GRASP2 metabQTL
High-grade glioma 4.3×10-4 19578366 (PMID) GRASP2 nonQTL