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

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Locus annotations

Locus 113

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
Mn SOD trans Discovery rs2545801 5:176,841,339 C/T 0.25 997 -0.606 0.046 4.6×10-36 -1.130 7×10-35 2.5×10-33

 

Regional association plots

Superoxide dismutase [Mn], mitochondrial (Mn SOD)

Download the association data used to generate this plot

 

Boxplots and histograms for top associations

Superoxide dismutase [Mn], mitochondrial (Mn SOD)

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

Superoxide dismutase [Mn], mitochondrial (Mn SOD)

Target (abbrv.) Mn SOD
Target (full name) Superoxide dismutase [Mn], mitochondrial
Somalogic ID (Sequence ID) SL001815 (5008-51_1)
Entrez Gene Symbol SOD2
UniProt ID P04179
UniProt Comment
  • Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.
Biomarker applications (based on IPA annotation)
  • diagnosis
  • unspecified application
Wiki Pathways
  • DNA damage response (only ATM dependent)
  • Folate Metabolism
  • Oxidative Stress
  • Selenium Pathway
  • Vitamin B12 Metabolism
Pathway Interaction Database
  • FoxO family signaling
Reactome
  • Detoxification of Reactive Oxygen Species

All locus annotations are based on the sentinel SNP (rs2545801) and 4 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
  • GRK6 G protein-coupled receptor kinase 6
  • F12 coagulation factor XII (Hageman factor)
Potentially regulated genes
  • F12 coagulation factor XII (Hageman factor)
  • F12
eQTL genes
  • RGS14 regulator of G-protein signaling 14
  • RAB24 RAB24, member RAS oncogene family
  • F12 coagulation factor XII (Hageman factor)
  • MXD3 MAX dimerization protein 3
  • GRIN2B glutamate receptor, ionotropic, N-methyl D-aspartate 2B

 

Results from other genome-wide association studies

Trait P Study Source
Factor XII antigen 1.3×10-115 23381943 (PMID) GRASP2 nonQTL
Activated partial thromboplastin time 6×10-88 22703881 (PMID) GWAS Catalog via SNiPA
Circulating vasoactive peptide levels 1×10-67 23381795 (PMID) GWAS Catalog via SNiPA
plasma levels of midregional-proadrenomedullin and C-terminal-pro-endothelin-1 1.3×10-67 23381795 (PMID) GRASP2 nonQTL
F12 gene expression in liver tissue 6.1×10-53 21602305 (PMID) GRASP2 eQTL
Activated Partial Thromboplastin Time 3×10-37 20303064 (PMID) GRASP2 nonQTL
Blood metabolite ratios 6×10-26 24816252 (PMID) GWAS Catalog via SNiPA
Gene expression of F12 in liver 1.2×10-23 18462017 (PMID) GRASP2 eQTL
bradykinin, des-arg(9) 2.8×10-23 24816252 (PMID) gwas.eu via SNiPA
Gene expression of RAB24 in blood 3×10-18 21829388 (PMID) GRASP2 eQTL
Activated Partial Thromboplastin Time (Female) 1.2×10-16 20303064 (PMID) GRASP2 nonQTL
"Gene expression of F12 [transcript NM_000505, probe A_23_P167674] in liver" 2×10-16 21637794 (PMID) GRASP2 eQTL
Activated Partial Thromboplastin Time (Male) 2.1×10-15 20303064 (PMID) GRASP2 nonQTL
Metabolite levels 3×10-14 22916037 (PMID) GWAS Catalog via SNiPA
Serum metabolite network profiles 3.2×10-14 22916037 (PMID) GRASP2 metabQTL
Serum Phe 4.6×10-11 22286219 (PMID) GRASP2 metabQTL
Serum Ala/Phe 6.1×10-11 22286219 (PMID) GRASP2 metabQTL
Gene expression of RHPN1 in liver 1.8×10-9 18462017 (PMID) GRASP2 eQTL
Gene expression of AC146507.3///MXD3 in blood 3.5×10-7 21829388 (PMID) GRASP2 eQTL
Platelet function and related traits 1×10-6 21546496 (PMID) GWAS Catalog via SNiPA
F12 levels 1.1×10-6 21546496 (PMID) GRASP2 nonQTL
Coronary artery disease (CAD) 2.7×10-6 21378988 (PMID) GRASP2 nonQTL
Gene expression of F12 [probe ILMN_12933] in untreated osteoblasts 8.1×10-6 21283786 (PMID) GRASP2 eQTL
Height 9.5×10-6 25282103 (PMID) Supplemental file
cg03871251 (chr5:176757694) 3.4×10-5 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
"Gene expression of PFN3 [transcript NM_001029886, probe A_24_P49997] in liver" 4.5×10-4 21637794 (PMID) GRASP2 eQTL

Possible link of SOD2 to kallikrein-kinin system

Trans-association with Superoxide dismutase [Mn], mitochondrial (SOD2). Replication in QMDiab not attempted due to lack of a tagging SNP. Genetic variant in cis impacts factor XII levels (not in SOMAscan panel). Verweij et al. [PubMed] report a "Genome-wide association study on plasma levels of midregional-proadrenomedullin and C-terminal-pro-endothelin-1" and state "The minor variants in KLKB1 (rs4253238) and F12 (rs2731672), both part of the kallikrein-kinin system, were associated with higher MR-pro-ADM (P=4.46E-52 and P=5.90E-24, respectively) and higher CT-pro-ET-1 levels (P=1.23E-122 and P=1.26E-67, respectively). Epistasis analyses showed a significant interaction between the sentinel SNP of F12 and KLKB1 for both traits." Link to SOD2 not clear. Confirms strong GWAS hits. Endothelin-1 (ET-1) and adrenomedullin (ADM) are circulating vasoactive peptides and predictors of cardiac death and heart failure.

The information gathered here is a result of an attempt to keep track of all interesting information that we encountered while investigating these loci. Please bear in mind that the annotation given here is neither complete nor free of errors, and that all information provided here should be confirmed by additional literature research before being used as a basis for firm conclusions or further experiments.