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

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Locus annotations

Locus 237

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
IMDH2 trans Discovery rs1005776 14:102,896,673 G/A 0.30 997 0.399 0.046 3.2×10-17 1.050 2.9×10-13 2×10-8
IMDH2 trans Replication rs1005776 14:102,896,673 G/A 0.36 337 0.105 0.048 0.028 1.020 0.115 0.398

 

Regional association plots

Inosine-5'-monophosphate dehydrogenase 2 (IMDH2)

Download the association data used to generate this plot

 

Boxplots and histograms for top associations

Inosine-5'-monophosphate dehydrogenase 2 (IMDH2)

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

Inosine-5'-monophosphate dehydrogenase 2 (IMDH2)

Target (abbrv.) IMDH2
Target (full name) Inosine-5'-monophosphate dehydrogenase 2
Somalogic ID (Sequence ID) SL010928 (5250-53_3)
Entrez Gene Symbol IMPDH2
UniProt ID P12268
UniProt Comment
  • Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.
Targeted by drugs (based on IPA annotation)
  • thioguanine
  • VX-944
  • pegintron/ribavirin
  • interferon alfa-2b/ribavirin
  • mycophenolate mofetil
  • mycophenolic acid
  • ribavirin

All locus annotations are based on the sentinel SNP (rs1005776) and 20 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


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Genes hit or close-by
  • AL137229.1
  • ZNF839 zinc finger protein 839
  • CINP cyclin-dependent kinase 2 interacting protein
  • TECPR2 tectonin beta-propeller repeat containing 2
eQTL genes
  • TECPR2 tectonin beta-propeller repeat containing 2
  • ANKRD9 ankyrin repeat domain 9
  • CINP cyclin-dependent kinase 2 interacting protein
  • ZNF839 zinc finger protein 839

 

Results from other genome-wide association studies

Trait P Study Source
Gene expression of ANKRD9 in blood 1.9×10-23 21829388 (PMID) GRASP2 eQTL
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 2.9×10-6 20502693 (PMID) GRASP2 eQTL
Differential exon level expression of KIAA0329 [probe 3553212] in brain cortex 6×10-6 19222302 (PMID) GRASP2 eQTL

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.