Connecting genetic risk to disease endpoints through the human blood plasma proteome
ONLINE SUPPLEMENTARY INFORMATION
Locus 269
Top associations per target
| Target | cis/trans | Study | SNP | SNP location | Maj/min allele | MAF | N | βinv | seinv | Pinv | fclog | Plog | Praw |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| sTie-1 | trans | Discovery | rs630510 | 9:136,149,581 | G/A | 0.47 | 994 | -0.350 | 0.043 | 1.6×10-15 | -1.060 | 5.4×10-15 | 8.5×10-15 |
| sTie-1 | trans | Replication | rs630014 | 9:136,149,722 | G/A | 0.44 | 337 | -0.392 | 0.060 | 2.4×10-10 | -1.100 | 6.1×10-10 | 6.4×10-10 |
Regional association plots
Tyrosine-protein kinase receptor Tie-1, soluble (sTie-1)
Boxplots and histograms for top associations
Tyrosine-protein kinase receptor Tie-1, soluble (sTie-1)
| Target (abbrv.) | sTie-1 |
| Target (full name) | Tyrosine-protein kinase receptor Tie-1, soluble |
| Somalogic ID (Sequence ID) | SL003199 (2844-53_2) |
| Entrez Gene Symbol | TIE1 |
| UniProt ID | P35590 |
| UniProt Comment |
|
All locus annotations are based on the sentinel SNP (rs630510) and 3 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 |
|
| Potentially regulated genes | |
| eQTL genes |
Results from other genome-wide association studies
| Trait | P | Study | Source |
|---|---|---|---|
| von Willebrand factor (vWF) | 6.7×10-87 | 21534939 (PMID) | GRASP2 nonQTL |
| Activated partial thromboplastin time | 1.9×10-46 | 22703881 (PMID) | GRASP2 nonQTL |
| Soluble intercellular adhesion molecule 1 (ICAM-1) | 1.5×10-22 | 21533024 (PMID) | GRASP2 nonQTL |
| Venous thrombosis | 2.5×10-19 | 21980494 (PMID) | GRASP2 nonQTL |
| TNF-alpha (TNF-a) | 5.4×10-17 | 18464913 (PMID) | GRASP2 nonQTL |
| LDL cholesterol | 2.1×10-16 | 24097068 (PMID) | Supplemental file |
| Triglycerides | 6.4×10-16 | 24097068 (PMID) | Supplemental file |
| Gene expression of MED22 in blood | 4.7×10-15 | 21829388 (PMID) | GRASP2 eQTL |
| Factor XIII antigen | 1.7×10-14 | 23381943 (PMID) | GRASP2 nonQTL |
| Gene expression of ABO (probeID ILMN_1656979) in temporal cortex in Alzheimer's disease cases and controls | 7.9×10-13 | 22685416 (PMID) | GRASP2 eQTL |
| Serum soluble E-selectin | 9.6×10-13 | 19729612 (PMID) | GRASP2 nonQTL |
| E-selectin | 9.7×10-13 | pha002871 (dbGaP) | dbGaP via SNiPA |
| Interleukin-6 (IL-6) levels | 1.1×10-9 | 22291609 (PMID) | GRASP2 nonQTL |
| ADpSGEGDFXAEGGGVR* | 3.5×10-9 | 24816252 (PMID) | gwas.eu via SNiPA |
| cg06818865 (chr9:136151982) | 4.8×10-9 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| Gene expression of ABO in normal prepouch ileum | 6.6×10-9 | 23474282 (PMID) | GRASP2 eQTL |
| Gene expression of SURF6 in blood | 1.2×10-8 | 21829388 (PMID) | GRASP2 eQTL |
| Venous thromboembolism (VTE) | 1.2×10-8 | 19278955 (PMID) | GRASP2 nonQTL |
| Circulating galectin-3 levels | 2.8×10-8 | 23056639 (PMID) | GRASP2 nonQTL |
| Hematocrit (Hct) | 3.7×10-8 | 23222517 (PMID) | GRASP2 nonQTL |
| Venous thromboembolism | 3.9×10-8 | 22672568 (PMID) | GRASP2 nonQTL |
| Pancreatic cancer | 6.3×10-8 | 19648918 (PMID) | GRASP2 nonQTL |
| Total cholesterol | 1.2×10-7 | 23063622 (PMID) | GRASP2 nonQTL |
| Pancreatic neoplasms | 4.7×10-6 | pha002889 (dbGaP) | dbGaP via SNiPA |
| Graves' disease | 8.2×10-6 | 23612905 (PMID) | GRASP2 nonQTL |
| Grave's disease | 8.5×10-6 | 21841780 (PMID) | GRASP2 nonQTL |
| Simpson-Angus Scale | 9.8×10-6 | 19875103 (PMID) | GRASP2 nonQTL |
| Gene expression of ABO (probeID ILMN_1656979) in cerebellum in Alzheimer's disease cases and controls | 1.1×10-5 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of SURF1 [probe ILMN_2148] in osteoblasts treated with dexamethasone | 1.8×10-5 | 21283786 (PMID) | GRASP2 eQTL |
| cg13660174 (chr9:136238416) | 7.8×10-5 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| Coronary artery disease (CAD) | 1.1×10-4 | 23202125 (PMID) | GRASP2 nonQTL |
| Coronary artery disease and myocardial infarction | 2.5×10-4 | 23202125 (PMID) | Supplemental file |
The pleiotropic ABO locus is discussed in the main paper.
This locus is discussed in the main paper. Here we report observations not mentioned in the paper: In Shin et al. [PubMed] SNP rs651007 associates with dipeptide levels (aspartylphenylalanine, p=2×10-7; X-14189, annotated as potential Leu-Ala, but Ser-Pro is also possible by mass alone, p=9.6×10-10; X14304, I/L-Ala or Ala-I/L?, p=1.8×10-8; X-14208, could be Cys-Met or Tyr-Ala or His-Pro or Ser-Phe by mass alone, p=1.5×10-7; X-14205; X14086: annotated as Thr-Glu, but mass is 25 too high; Val-Arg possible by mass alone). This SNP also associates in Raffler et al. [PubMed] (Urine NMR) with a signal at 2.0308 ppm (PM20308, p=5.1×10-20). It is also a marginal hit in CardioGram (7.1×10-8). He et al. [PubMed] report a genome wide association study of genetic loci that influence tumour biomarkers cancer antigen 19-9, carcinoembryonic antigen and α fetoprotein and their associations with cancer risk. The authors find strong association of SNP rs8176749 with carcinoembryonic antigen (CEA) levels – we find association with Cadherin-5. CD209 and MBL2 are both lectins. All associated ABO-associated proteins are glycoproteins, part of glycoprotein complex (LY96), or glycoprotein-binding (SELE), except for IL27RA (http://jcggdb.jp/rcmg/gpdb/index). According to Uniprot all proteins are glycoproteins (including associations non-replicated in QMDiab), while only half of all SomaLogic proteins are glycoproteins. The Panther classification system (http://pantherdb.org/tools/compareToRefList.jsp) reported a significant enrichment of the GO process "endothelial cell differentiation" (GO:0045446): 5 out of 17 annotated proteins were found (expected were 0.32, p=1.45×10-5). 
Subnetwork of the ABO locus.Six replicated pQTLs at the ABO gene locus (red), including SNP identifiers that are linked to the the six loci (light green KORA SNPs, yellow QMDiab SNPs, bright green both), pQTLS (blue), proteins with significant partial correlation are connected, associations with GWAS endpoints are shown (grey) [NOTE: the anorexia is a false positive, checked this with the consortium].
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.