Connecting genetic risk to disease endpoints through the human blood plasma proteome
ONLINE SUPPLEMENTARY INFORMATION
Locus 195
Top associations per target
| Target | cis/trans | Study | SNP | SNP location | Maj/min allele | MAF | N | βinv | seinv | Pinv | fclog | Plog | Praw |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BST1 | cis | Discovery | rs1789 | 4:15,664,535 | A/G | 0.36 | 995 | 0.414 | 0.044 | 4.5×10-20 | 1.240 | 2.6×10-22 | 3.4×10-22 |
| BST1 | cis | Replication | rs10008376 | 4:15,623,955 | A/G | 0.48 | 337 | 0.369 | 0.059 | 1.5×10-9 | 1.300 | 1.5×10-10 | 1.5×10-9 |
Regional association plots
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 (BST1)
Boxplots and histograms for top associations
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 (BST1)
| Target (abbrv.) | BST1 |
| Target (full name) | ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 |
| Somalogic ID (Sequence ID) | SL008644 (4535-50_2) |
| Entrez Gene Symbol | BST1 |
| UniProt ID | Q10588 |
| UniProt Comment |
|
All locus annotations are based on the sentinel SNP (rs1789) and 44 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 |
|---|---|---|---|
| cg18470593 (chr4:15471353) | 1.4×10-234 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| cg21329975 (chr4:15471190) | 4.7×10-228 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| cg21123203 (chr4:15471277) | 1.6×10-111 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| Gene expression of FBXL5 in blood | 2.2×10-66 | 21829388 (PMID) | GRASP2 eQTL |
| cg02630888 (chr4:15657844) | 1.4×10-60 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| Gene expression of FBXL5 (probeID ILMN_1673370) in breast tumors | 3.4×10-25 | 22522925 (PMID) | GRASP2 eQTL |
| cg00076653 (chr4:15341854) | 2.2×10-21 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| cg24225360 (chr4:15471675) | 4.8×10-21 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| Gene expression of FBXL5 in liver | 7.6×10-19 | 18462017 (PMID) | GRASP2 eQTL |
| Gene expression of FBXL5 [probe 209005_at] in lymphoblastoid cell lines | 1×10-12 | 17873877 (PMID) | GRASP2 eQTL |
| cg10494397 (chr4:15593830) | 6.2×10-12 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| Gene expression of FBXL5 (probeID ILMN_1673370) in temporal cortex in Alzheimer's disease cases and controls | 3.9×10-11 | 22685416 (PMID) | GRASP2 eQTL |
| cg18334727 (chr4:15659888) | 6.7×10-11 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| cg11290265 (chr4:15375842) | 1.6×10-7 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| Gene expression of BST1 in normal prepouch ileum | 2.3×10-7 | 23474282 (PMID) | GRASP2 eQTL |
| Gene expression of FBXL5 (probeID ILMN_1673370) in cerebellum in Alzheimer's disease cases and controls | 1.4×10-6 | 22685416 (PMID) | GRASP2 eQTL |
| Gene expression of FBXL5 (ENSG00000118564) in dendritic cells | 3.8×10-6 | 22233810 (PMID) | GRASP2 eQTL |
| Serum ratio of (linoleate (18:2n6))/(oleoylcarnitine) | 5.4×10-6 | 21886157 (PMID) | GRASP2 metabQTL |
| Serum ratio of (1-docosahexaenoylglycerophosphocholine*)/(1-palmitoleoylglycerophosphocholine*) | 1.4×10-5 | 21886157 (PMID) | GRASP2 metabQTL |
| Serum concentration of 2-tetradecenoyl carnitine | 2×10-5 | 21886157 (PMID) | GRASP2 metabQTL |
| Height | 3.7×10-5 | 25282103 (PMID) | Supplemental file |
| Serum concentration of 7-methylguanine | 3.8×10-5 | 21886157 (PMID) | GRASP2 metabQTL |
| palmitoyl sphingomyelin | 6.9×10-5 | 24816252 (PMID) | gwas.eu via SNiPA |
| Gene expression of FBXL5 in CD4+ lymphocytes | 6.9×10-5 | 20833654 (PMID) | GRASP2 eQTL |
| Hypertension, combined control dataset | 8.1×10-5 | 17554300 (PMID) | GRASP2 nonQTL |
| Coronary artery disease (CAD) | 3.9×10-4 | 23202125 (PMID) | GRASP2 nonQTL |
| Coronary artery disease and myocardial infarction | 3.9×10-4 | 23202125 (PMID) | Supplemental file |
Near total protein loss of BST1 in homozygotes of certain minor allele variants.
Multiple replicated cis-pQTLs to ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 2 (BST1). BST1 is an extracellularly exposed enzyme that possesses Cyclic ADP ribose (cADPR) hydrolase activity. cAD is a second messenger that releases calcium from intracellular calcium stores. BST1 is mainly expressed in the bone marrow. It appears that the minor allele variants of both, rs2302465 (Locus 18) and rs7657257 (Locus 151), tag haplotypes that carry the same functional variant, and which leads to full loss of BST1. Using imputed data a number of highly significant SNPs were identified, i.e. SNP rs73224659 (p=4.0×10-179 compared to p=1.5×10-108 for rs2302465). Minor allele carriers of rs73224659 show nearly no protein levels of BST1.
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.