HelmholtzZentrum munich
WCMC

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

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 76

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
Hemopexin trans Discovery rs10801582 1:196,944,357 G/A 0.23 997 -0.737 0.047 1.1×10-49 -1.480 1.2×10-43 7.8×10-50
Hemopexin trans Replication rs7531555 1:196,929,310 G/A 0.32 337 -0.535 0.077 2×10-11 -1.380 1.1×10-11 2.9×10-11

 

Regional association plots

 

Boxplots and histograms for top associations

Hemopexin

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

Hemopexin

Target (abbrv.) Hemopexin
Target (full name) Hemopexin
Somalogic ID (Sequence ID) SL000440 (2768-56_2)
Entrez Gene Symbol HPX
UniProt ID P02790
UniProt Comment
  • Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation.
Reactome
  • Scavenging of heme from plasma

All locus annotations are based on the sentinel SNP (rs10801582) and 17 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
eQTL genes
  • CFHR4 complement factor H-related 4
  • CFHR1 complement factor H-related 1
  • CFHR3 complement factor H-related 3
  • CFH complement factor H

 

Results from other genome-wide association studies

Trait P Study Source
Advanced age-related macular degeneration 8.1×10-105 23455636 (PMID) GRASP2 nonQTL
Advanced age-related macular degeneration (choroidal neovascularization) vs. no AMD 2.1×10-59 23455636 (PMID) GRASP2 nonQTL
Advanced age-related macular degeneration (geographic atrophy) 1×10-45 23455636 (PMID) GRASP2 nonQTL
Macular degeneration 5.9×10-34 pha002869 (dbGaP) dbGaP via SNiPA
cg05439665 (chr13:113656400) 4.9×10-25 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg04907151 (chr3:135684185) 3.6×10-24 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg05315334 (chr13:113656188) 5.8×10-22 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg07038400 (chr3:135684187) 1.3×10-20 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Factor XIII A subunit 3.9×10-19 23381943 (PMID) GRASP2 nonQTL
End-stage coagulation 7×10-19 23381943 (PMID) GWAS Catalog via SNiPA
cg21094405 (chr13:113656093) 1.3×10-17 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Factor XIII B subunit 5.8×10-17 23381943 (PMID) GRASP2 nonQTL
cg18804667 (chr5:58883416) 2×10-14 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Factor XIII activity 4.3×10-12 23381943 (PMID) GRASP2 nonQTL
Age-related macular degeneration 5.2×10-12 23577725 (PMID) GRASP2 nonQTL
cg09357934 (chr2:159651942) 2.9×10-11 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg05593411 (chr5:58883454) 4.9×10-11 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg21992932 (chr2:159651837) 7.8×10-11 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg12549300 (chr13:113594752) 6×10-9 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg23560546 (chr2:159652043) 1.1×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Age-related macular degeneration (Stage 5 ARMD) 2.1×10-8 23577725 (PMID) GRASP2 nonQTL
cg16169675 (chr13:113594698) 2.3×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg24362661 (chr1:871570) 4.2×10-8 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
cg09863772 (chr2:11886424) 1.1×10-7 10.1101/033084 (DOI) BIOS QTL trans-meQTLs
Age-related macular degeneration in ever smokers 4.3×10-5 23577725 (PMID) GRASP2 nonQTL
Serum ratio of (1,6-anhydroglucose)/(pipecolate) 1.5×10-4 21886157 (PMID) GRASP2 metabQTL
Serum ratio of (arabinose)/(taurolithocholate 3-sulfate) 2.1×10-4 21886157 (PMID) GRASP2 metabQTL
Age-related macular degeneration in never smokers 2.9×10-4 23577725 (PMID) GRASP2 nonQTL

CFHR4 may regulate HPX protein levels.

This locus is discussed in the main paper.

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.