Connecting genetic risk to disease endpoints through the human blood plasma proteome
ONLINE SUPPLEMENTARY INFORMATION
Locus annotations
Locus 106
Top associations per target
| Target | cis/trans | Study | SNP | SNP location | Maj/min allele | MAF | N | βinv | seinv | Pinv | fclog | Plog | Praw |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Protein C | trans | Discovery | rs867186 | 20:33,764,554 | A/G | 0.12 | 997 | 0.838 | 0.062 | 5.5×10-38 | 1.130 | 7.8×10-27 | 1.4×10-35 |
| Protein C | trans | Replication | rs867186 | 20:33,764,554 | A/G | 0.11 | 337 | 0.910 | 0.084 | 9×10-24 | 1.180 | 5.7×10-22 | 1.3×10-25 |
Regional association plots
Vitamin K-dependent protein C (Protein C)
Boxplots and histograms for top associations
Vitamin K-dependent protein C (Protein C)
| Target (abbrv.) | Protein C |
| Target (full name) | Vitamin K-dependent protein C |
| Somalogic ID (Sequence ID) | SL000048 (2961-1_2) |
| Entrez Gene Symbol | PROC |
| UniProt ID | P04070 |
| UniProt Comment | |
| Biomarker applications (based on IPA annotation) |
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| Wiki Pathways |
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| Pathway Interaction Database |
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| Reactome |
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| Pathway Studio |
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All locus annotations are based on the sentinel SNP (rs867186) and 167 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 |
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| Potentially regulated genes |
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| eQTL genes |
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Results from other genome-wide association studies
| Trait | P | Study | Source |
|---|---|---|---|
| Plasma protein-C levels | 2.7×10-203 | 20802025 (PMID) | GRASP2 nonQTL |
| Protein C levels | 2×10-200 | 20802025 (PMID) | GWAS Catalog via SNiPA |
| Gene expression of EIF6 in blood | 2.6×10-46 | 21829388 (PMID) | GRASP2 eQTL |
| FVII | 2.2×10-38 | 21676895 (PMID) | GRASP2 nonQTL |
| FVII activity | 2.4×10-37 | 21676895 (PMID) | GRASP2 nonQTL |
| FVII in plasma | 5.7×10-37 | 20231535 (PMID) | GRASP2 nonQTL |
| Coagulation factor levels | 6×10-37 | 20231535 (PMID) | GWAS Catalog via SNiPA |
| Hemostatic factors and hematological phenotypes | 4×10-34 | 22443383 (PMID) | GWAS Catalog via SNiPA |
| Plasma protein C levels in venous thrombosis | 4.2×10-31 | 22443383 (PMID) | GRASP2 nonQTL |
| Gene expression of ITGB4BP in peripheral blood monocytes | 5.3×10-24 | 20502693 (PMID) | GRASP2 eQTL |
| Gene expression of MYH7B///TRPC4AP in blood | 8.6×10-23 | 21829388 (PMID) | GRASP2 eQTL |
| Gene expression of EIF6 in peripheral blood monocytes | 1.9×10-22 | 20502693 (PMID) | GRASP2 eQTL |
| cg11320187 (chr20:33578118) | 2.7×10-20 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| cg18215705 (chr20:33449053) | 5.3×10-18 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| cg00952050 (chr20:33585016) | 5.3×10-16 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| cg12303736 (chr4:165953282) | 4.5×10-14 | 10.1101/033084 (DOI) | BIOS QTL trans-meQTLs |
| Prothrombin time | 5×10-13 | 22703881 (PMID) | GWAS Catalog via SNiPA |
| Prothrombin time by INR (international normalized ratio) | 5.3×10-13 | 22703881 (PMID) | GRASP2 nonQTL |
| "Gene expression of PROCR [transcript NM_006404, probe A_23_P80040] in liver" | 1.2×10-11 | 21637794 (PMID) | GRASP2 eQTL |
| Normalized agkistrodon contortrix venom ratio in venous thrombosis | 2.7×10-11 | 22443383 (PMID) | GRASP2 nonQTL |
| cg25513321 (chr20:33577034) | 9.8×10-11 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| Height | 2.1×10-10 | 25282103 (PMID) | Supplemental file |
| Plasma protein C levels | 3.9×10-9 | 22216198 (PMID) | GRASP2 nonQTL |
| Anticoagulant levels | 4×10-9 | 22216198 (PMID) | GWAS Catalog via SNiPA |
| Coronary artery disease (CAD) | 3.2×10-8 | 21966275 (PMID) | GRASP2 nonQTL |
| Coronary artery disease and myocardial infarction | 1.4×10-7 | 23202125 (PMID) | Supplemental file |
| Gene expression of PROCR (probeID ILMN_1717262) in breast tumors | 2×10-7 | 22522925 (PMID) | GRASP2 eQTL |
| cg11231913 (chr20:33577505) | 5.4×10-7 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| Gene expression of CPNE1 in peripheral blood monocytes | 1.7×10-6 | 20502693 (PMID) | GRASP2 eQTL |
| Plasma fibrin D-dimer levels | 3.7×10-6 | 21502573 (PMID) | GRASP2 nonQTL |
| Amyotrophic lateral sclerosis (sporadic) | 4×10-6 | 24529757 (PMID) | GWAS Catalog via SNiPA |
| D-dimer levels | 4×10-6 | 21502573 (PMID) | GWAS Catalog via SNiPA |
| Gene expression of UQCC in peripheral blood monocytes | 9.1×10-6 | 20502693 (PMID) | GRASP2 eQTL |
| Gene expression of PROCR (probeID ILMN_1717262) in cerebellum in Alzheimer's disease cases and controls | 9.7×10-6 | 22685416 (PMID) | GRASP2 eQTL |
| cg06244927 (chr20:33590016) | 1.3×10-5 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| Beta-amyloid peptide (Abeta1-42) in cerebrospinal fliud in mild cognitive impairment subjects | 6.5×10-5 | 20932310 (PMID) | GRASP2 nonQTL |
| Gene expression of GGT7 in liver | 8.3×10-5 | 21637794 (PMID) | GRASP2 eQTL |
| Cognitive response to topiramate treatment as measured by the Controlled Oral Word Association cognitive test | 8.7×10-5 | 22091778 (PMID) | GRASP2 nonQTL |
Replicates GWAS hit with Protein C levels.
This locus harbours a replicated trans-pQTL with Vitamin K-dependent protein C (PROC), association with CVD in CardioGram with p=1.36×10-7, other GWAS hits at this locus are with a number of coagulation parameters. The receptor of PROC (PROCR) is encoded at this locus. The sentinel SNP rs867186 is a G/S amino acid exchange. Tang et al. [PubMed] already reported a strong association of variance in PROCR with PROC levels.
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.