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

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Locus annotations

Locus 249

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
TIG2 cis Discovery rs9640161 7:150,045,910 C/A 0.37 987 0.347 0.042 3×10-16 1.070 2.4×10-15 1.7×10-13
TIG2 cis Replication rs3735167 7:150,039,555 G/A 0.25 337 0.255 0.079 0.001 1.050 0.001 0.002

 

Regional association plots

Retinoic acid receptor responder protein 2 (TIG2)

Download the association data used to generate this plot

 

Boxplots and histograms for top associations

Retinoic acid receptor responder protein 2 (TIG2)

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

Retinoic acid receptor responder protein 2 (TIG2)

Target (abbrv.) TIG2
Target (full name) Retinoic acid receptor responder protein 2
Somalogic ID (Sequence ID) SL005152 (3079-62_2)
Entrez Gene Symbol RARRES2
UniProt ID Q99969
UniProt Comment
  • Adipocyte-secreted protein (adipokine) that regulates adipogenesis, metabolism and inflammation through activation of the chemokine-like receptor 1 (CMKLR1). Its other ligands include G protein-coupled receptor 1 (GPR1) and chemokine receptor-like 2 (CCRL2). Positively regulates adipocyte differentiation, modulates the expression of adipocyte genes involved in lipid and glucose metabolism and might play a role in angiogenesis, a process essential for the expansion of white adipose tissue. Also acts as a proinflammatory adipokine, causing an increase in secretion of proinflammatory and prodiabetic adipokines, which further impair adipose tissue metabolic function and have negative systemic effects including impaired insulin sensitivity, altered glucose and lipid metabolism, and a decrease in vascular function in other tissues. Can have both pro- and anti-inflammatory properties depending on the modality of enzymatic cleavage by different classes of proteases. Acts as a chemotactic factor for leukocyte populations expressing CMKLR1, particularly immature plasmacytoid dendritic cells, but also immature myeloid DCs, macrophages and natural killer cells. Exerts an anti-inflammatory role by preventing TNF/TNFA-induced VCAM1 expression and monocytes adhesion in vascular endothelial cells. The effect is mediated via inhibiting activation of NF-kappa-B and CRK/p38 through stimulation of AKT1/NOS3 signaling and nitric oxide production. Its dual role in inflammation and metabolism might provide a link between chronic inflammation and obesity, as well as obesity-related disorders such as type 2 diabetes and cardiovascular disease. Exhibits an antimicrobial function in the skin.

All locus annotations are based on the sentinel SNP (rs9640161) and 2 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
  • LRRC61 leucine rich repeat containing 61
  • ZBED6CL ZBED6 C-terminal like
eQTL genes

 

Results from other genome-wide association studies

Trait P Study Source
Methylation levels at chr7:149657614-149657664 [hg18 coord, probe cg12556325] in Caudal pons 7.6×10-15 20485568 (PMID) GRASP2 meQTL
Methylation levels at chr7:149657614-149657664 [hg18 coord, probe cg12556325] in Temporal cortex 5.2×10-13 20485568 (PMID) GRASP2 meQTL
Methylation levels at chr7:149657933-149657983 [hg18 coord, probe cg04999691] in Cerebellum 1.1×10-12 20485568 (PMID) GRASP2 meQTL
Methylation levels at chr7:149657614-149657664 [hg18 coord, probe cg12556325] in Frontal cortex 1.6×10-10 20485568 (PMID) GRASP2 meQTL
Gene expression of LRRC61 (probeID ILMN_1669722) in cerebellum in Alzheimer's disease cases and controls 3.6×10-9 22685416 (PMID) GRASP2 eQTL
Gene expression of RARRES2 in CEU-CHB-JPT lymphoblastoid cell lines 5.2×10-9 17873874 (PMID) GRASP2 eQTL
Gene expression of LRRC61 (probeID ILMN_1669722) in cerebellum in non-Alzheimer's disease samples 8.8×10-7 22685416 (PMID) GRASP2 eQTL