Connecting genetic risk to disease endpoints through the human blood plasma proteome
ONLINE SUPPLEMENTARY INFORMATION
Locus 108
Top associations per target
| Target | cis/trans | Study | SNP | SNP location | Maj/min allele | MAF | N | βinv | seinv | Pinv | fclog | Plog | Praw |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| IMDH1 | trans | Discovery | rs1190552 | 14:102,911,907 | G/A | 0.23 | 994 | 0.654 | 0.049 | 1.5×10-37 | 1.240 | 1.3×10-22 | 0.093 |
| IMDH1 | trans | Replication | rs1190552 | 14:102,911,907 | G/A | 0.30 | 337 | 0.270 | 0.072 | 2×10-4 | 1.090 | 0.036 | 0.476 |
Regional association plots
Inosine-5'-monophosphate dehydrogenase 1 (IMDH1)
Boxplots and histograms for top associations
Inosine-5'-monophosphate dehydrogenase 1 (IMDH1)
| Target (abbrv.) | IMDH1 |
| Target (full name) | Inosine-5'-monophosphate dehydrogenase 1 |
| Somalogic ID (Sequence ID) | SL014735 (5229-90_3) |
| Entrez Gene Symbol | IMPDH1 |
| UniProt ID | P20839 |
| UniProt Comment |
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| Targeted by drugs (based on IPA annotation) |
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All locus annotations are based on the sentinel SNP (rs1190552) and 36 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 |
|---|---|---|---|
| cg03240324 (chr14:102974801) | 2.7×10-15 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| Height | 4.1×10-14 | 25282103 (PMID) | Supplemental file |
| Gene expression of ANKRD9 in peripheral blood monocytes | 2.6×10-9 | 20502693 (PMID) | GRASP2 eQTL |
| Differential exon level expression of KIAA0329 [probe 3553212] in brain cortex | 1.8×10-8 | 19222302 (PMID) | GRASP2 eQTL |
| cg00252594 (chr14:102974761) | 2.8×10-8 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
| cg06761850 (chr14:102904445) | 1.4×10-7 | 10.1101/033084 (DOI) | BIOS QTL cis-meQTLs |
Possible link to cell cycle control, may play a role in genetic association with body height.
Two non-replicated trans-pQTLs (but both still nominally significant in QMDIab) with Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1) and Inosine-5'-monophosphate dehydrogenase 2 (IMPDH2). Both variants likely tag the same signal: rs1190552 and rs1005776 are in LD, r2=0.65, the association signal of IMPDH2 with rs1005776 and rs1190552 is comparable, that of IMPDH1 with SNPs rs1190552 is stronger). IMPDH1 and IMPDH2 regulate cell growth and catalyse the synthesis of xanthine monophosphate (XMP) from inosine-5'-monophosphate (IMP). This is the rate-limiting step in the de novo synthesis of guanine nucleotides. There is an eQTL with CDK2-interacting protein (CINP) at this locus. Lovejoy et al. [PubMed] identified CINP as a cell-cycle checkpoint protein, suggesting a possible link to cell cycle control. IMDH1 and IMDH2 physically interact. This association could also explain a GWAS hit with body height (p=4.1×10-14).
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.