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WCMC

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

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Locus annotations

Locus 259

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
C1s trans Discovery rs12734260 1:196,865,417 G/T 0.11 996 0.506 0.061 5.7×10-16 1.060 4×10-14 2.4×10-10
C1s trans Replication rs7522952 1:196,882,344 A/G 0.12 337 0.213 0.095 0.026 1.040 0.009 0.006

 

Regional association plots

 

Boxplots and histograms for top associations

Complement C1s subcomponent (C1s)

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

Complement C1s subcomponent (C1s)

Target (abbrv.) C1s
Target (full name) Complement C1s subcomponent
Somalogic ID (Sequence ID) SL000311 (3590-8_3)
Entrez Gene Symbol C1S
UniProt ID P09871
UniProt Comment
  • C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4.
Targeted by drugs (based on IPA annotation)
  • SERPING1
Wiki Pathways
  • Complement Activation, Classical Pathway
  • Complement and Coagulation Cascades
Reactome
  • Classical antibody-mediated complement activation
  • Initial triggering of complement
Pathway Studio
  • Classical Complement Pathway

All locus annotations are based on the sentinel SNP (rs12734260) and 69 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
  • KCNT2 potassium channel, sodium activated subfamily T, member 2
eQTL genes
  • CFHR1 complement factor H-related 1
  • CFHR3 complement factor H-related 3
  • CFH complement factor H
  • JUP junction plakoglobin
  • ZBTB41 zinc finger and BTB domain containing 41

 

Results from other genome-wide association studies

Trait P Study Source
Advanced age-related macular degeneration 1.4×10-73 23455636 (PMID) GRASP2 nonQTL
Advanced age-related macular degeneration (choroidal neovascularization) vs. no AMD 1.4×10-44 23455636 (PMID) GRASP2 nonQTL
Advanced age-related macular degeneration (geographic atrophy) 3.5×10-31 23455636 (PMID) GRASP2 nonQTL
Macular degeneration 4.9×10-21 pha002869 (dbGaP) dbGaP via SNiPA
Methylation levels at chr1:195010245-195010295 [hg18 coord, probe cg04614339] in Frontal cortex 2.6×10-17 20485568 (PMID) GRASP2 meQTL
Gene expression of CFHR3 in liver 1.1×10-13 22006096 (PMID) GRASP2 eQTL
Gene expression of CFHR1 in liver 2.5×10-13 22006096 (PMID) GRASP2 eQTL
Methylation levels at chr1:195010245-195010295 [hg18 coord, probe cg04614339] in Temporal cortex 5.1×10-13 20485568 (PMID) GRASP2 meQTL
Methylation levels at chr1:195010245-195010295 [hg18 coord, probe cg04614339] in Caudal pons 1.5×10-10 20485568 (PMID) GRASP2 meQTL
Age-related macular degeneration 6.5×10-10 23577725 (PMID) GRASP2 nonQTL
Methylation levels at chr1:195010245-195010295 [hg18 coord, probe cg04614339] in Cerebellum 2×10-9 20485568 (PMID) GRASP2 meQTL
Age-related macular degeneration (Stage 5 ARMD) 2.6×10-9 23577725 (PMID) GRASP2 nonQTL
Methylation levels at chr1:195054423-195054473 [hg18 coord, probe cg12687463] in Frontal cortex 9.7×10-9 20485568 (PMID) GRASP2 meQTL
Age-related macular degeneration in ever smokers 1.8×10-7 23577725 (PMID) GRASP2 nonQTL
Gene expression of ZDHHC22 in peripheral blood monocytes 1.9×10-6 20502693 (PMID) GRASP2 eQTL
HWESASXX* 1.7×10-5 24816252 (PMID) gwas.eu via SNiPA
Serum concentration of HWESASXX* 1.9×10-5 21886157 (PMID) GRASP2 metabQTL
Alzheimer's disease 1×10-4 24162737 (PMID) Supplemental file
Age-related macular degeneration in never smokers 1.8×10-4 23577725 (PMID) GRASP2 nonQTL

SOMAscan assay update regarding Complement C1s subcomponent

According to a SOMAscan assay change log issued on 12/22/2016, the SOMAmer reagent 3590-8 (targeting Complement C1s subcomponent) was removed from the SOMAscan panel for the following reason: "Mass spectrometry identifies Complement Factor H as the protein enriched from plasma when the SOMAmer reagent 3590-8 is used for affinity capture."