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

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Locus annotations

Locus 352

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
6Ckine trans Discovery rs17412738 3:132,257,419 A/G 0.12 991 -0.484 0.066 5.3×10-13 -1.130 8.3×10-12 2.6×10-9
6Ckine trans Replication rs11925382 3:132,219,554 A/G 0.17 337 -0.360 0.086 3.8×10-5 -1.120 1×10-4 0.003

 

Regional association plots

 

Boxplots and histograms for top associations

C-C motif chemokine 21 (6Ckine)

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

C-C motif chemokine 21 (6Ckine)

Target (abbrv.) 6Ckine
Target (full name) C-C motif chemokine 21
Somalogic ID (Sequence ID) SL003193 (2516-57_3)
Entrez Gene Symbol CCL21
UniProt ID O00585
UniProt Comment
  • Inhibits hemopoiesis and stimulates chemotaxis. Chemotactic in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Shows preferential activity towards naive T-cells. May play a role in mediating homing of lymphocytes to secondary lymphoid organs. Binds to atypical chemokine receptor ACKR4 and mediates the recruitment of beta-arrestin (ARRB1/2) to ACKR4.
Biomarker applications (based on IPA annotation)
  • disease progression
Reactome
  • Chemokine receptors bind chemokines
  • G alpha (i) signalling events

All locus annotations are based on the sentinel SNP (rs17412738) and 68 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
  • DNAJC13 DnaJ (Hsp40) homolog, subfamily C, member 13
  • NPHP3-ACAD11 NPHP3-ACAD11 readthrough (NMD candidate)
  • ACAD11 acyl-CoA dehydrogenase family, member 11
  • ACKR4 atypical chemokine receptor 4
  • HSPA8P19 heat shock 70kDa protein 8 pseudogene 19
  • UBA5 ubiquitin-like modifier activating enzyme 5
  • NPHP3 nephronophthisis 3 (adolescent)
Potentially regulated genes
  • DNAJC13 DnaJ (Hsp40) homolog, subfamily C, member 13
  • ACAD11 acyl-CoA dehydrogenase family, member 11
eQTL genes
  • NPHP3-AS1 NPHP3 antisense RNA 1
  • NPHP3 nephronophthisis 3 (adolescent)
  • DNAJC13 DnaJ (Hsp40) homolog, subfamily C, member 13

 

Results from other genome-wide association studies

Trait P Study Source
cg24577160 (chr3:132372241) 1.4×10-13 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
"Gene expression of NA probe[A_23_P108546],APOBEC1 probe[A_23_P14019],PCDH15 probe[A_23_P161331],NA probe[A_23_P202610],CDKL2 probe[A_23_P259270],ZFP42 probe[A_23_P259500],NA probe[A_23_P81888] in endometrial tumors" 7.3×10-10 21226949 (PMID) GRASP2 eQTL
LDL cholesterol 2×10-9 24097068 (PMID) Supplemental file
Gene expression of NPHP3 in peripheral blood monocytes 8.9×10-9 20502693 (PMID) GRASP2 eQTL
Gene expression of NPHP3 in blood 7.1×10-8 21829388 (PMID) GRASP2 eQTL
Triglycerides 5.3×10-7 24097068 (PMID) Supplemental file
Total cholesterol 8.4×10-7 20686565 (PMID) GRASP2 nonQTL
cg19770281 (chr3:132262017) 1.5×10-6 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
methionine 2.8×10-6 24816252 (PMID) gwas.eu via SNiPA
"Gene expression of CCRL1 [transcript NM_016557, probe A_23_P6909] in liver" 3.7×10-6 21637794 (PMID) GRASP2 eQTL
Gene expression of ACPP in peripheral blood monocytes 9.2×10-6 20502693 (PMID) GRASP2 eQTL
Height 1.7×10-5 25282103 (PMID) Supplemental file
Prostate cancer 3×10-5 20676098 (PMID) GRASP2 nonQTL
Waist circumfence, adjusted for BMI 4×10-5 25673412 (PMID) Supplemental file
Gene expression of CCRL1 [probe ILMN_7293] in osteoblasts treated with dexamethasone 4.1×10-5 21283786 (PMID) GRASP2 eQTL
Coronary artery disease 5.4×10-5 pha003031 (dbGaP) dbGaP via SNiPA
Coronary artery disease (CAD) 9.4×10-5 23202125 (PMID) GRASP2 nonQTL
Coronary artery disease and myocardial infarction 3.8×10-4 23202125 (PMID) Supplemental file
Pubertal growth, late adolescence 4.9×10-4 23449627 (PMID) Supplemental file

Possible link between cis-variants and protein levels of CCL21.

This locus harbours a replicated trans-pQTL to C-C motif chemokine 21 (CCL21).

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.