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

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Locus annotations

Locus 306

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
RUXF trans Discovery rs4420638 19:45,422,946 A/G 0.17 994 -0.435 0.056 3×10-14 -1.040 2.5×10-4 0.314
RUXF trans Replication rs4420638 19:45,422,946 A/G 0.12 337 -0.263 0.104 0.012 -1.050 0.031 0.126
Apo E2 cis Discovery rs4420638 19:45,422,946 A/G 0.17 994 0.419 0.056 1.9×10-13 1.070 1.9×10-12 1.5×10-13
Apo E2 cis Replication rs4420638 19:45,422,946 A/G 0.12 337 0.270 0.107 0.012 1.050 0.029 0.014

 

Regional association plots

Small nuclear ribonucleoprotein F (RUXF)

Download the association data used to generate this plot

Apolipoprotein E (isoform E2) (Apo E2)

Download the association data used to generate this plot

 

Boxplots and histograms for top associations

Small nuclear ribonucleoprotein F (RUXF)

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

Apolipoprotein E (isoform E2) (Apo E2)

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

Small nuclear ribonucleoprotein F (RUXF)

Target (abbrv.) RUXF
Target (full name) Small nuclear ribonucleoprotein F
Somalogic ID (Sequence ID) SL009790 (5494-52_3)
Entrez Gene Symbol SNRPF
UniProt ID P62306
UniProt Comment
  • Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Thereby, plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in an heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. As part of the U7 snRNP it is involved in histone 3'-end processing.
Wiki Pathways
  • mRNA processing
Reactome
  • Cleavage of Growing Transcript in the Termination Region
  • SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs
  • SLBP independent Processing of Histone Pre-mRNAs
  • mRNA Splicing - Major Pathway
  • mRNA Splicing - Minor Pathway
  • snRNP Assembly

Apolipoprotein E (isoform E2) (Apo E2)

Target (abbrv.) Apo E2
Target (full name) Apolipoprotein E (isoform E2)
Somalogic ID (Sequence ID) SL000277 (5312-49_3)
Entrez Gene Symbol APOE
UniProt ID P02649
UniProt Comment
  • Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand for the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues.
Biomarker applications (based on IPA annotation)
  • diagnosis
  • efficacy
  • prognosis
  • unspecified application
Wiki Pathways
  • Alzheimers Disease
  • Statin Pathway
  • Vitamin B12 Metabolism
Reactome
  • Chylomicron-mediated lipid transport
  • HDL-mediated lipid transport
  • Retinoid metabolism and transport
  • Scavenging by Class A Receptors

All locus annotations are based on the sentinel SNP (rs4420638) and 4 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

 

Results from other genome-wide association studies

Trait P Study Source
Alzheimer's disease 0×100 24162737 (PMID) Supplemental file
Late onset Alzheimer's disease 1×10-300 21460841 (PMID) GRASP2 nonQTL
LDL cholesterol 1.5×10-178 24097068 (PMID) Supplemental file
Cholesterol, total 1×10-149 24097068 (PMID) GWAS Catalog via SNiPA
Triglycerides 1.1×10-149 24097068 (PMID) Supplemental file
C-reactive protein (CRP) 8.8×10-139 21300955 (PMID) GRASP2 nonQTL
C-reactive protein levels 9×10-139 21300955 (PMID) GWAS Catalog via SNiPA
Total cholesterol 2.7×10-116 20686565 (PMID) GRASP2 nonQTL
Total cholesterol (females) 1×10-72 20686565 (PMID) GRASP2 nonQTL
Metabolic syndrome domains (Multivariate analysis) 1.7×10-57 22022282 (PMID) GRASP2 nonQTL
Alzheimer's disease (late onset) 1×10-39 17474819 (PMID) GWAS Catalog via SNiPA
Sporadic late onset Alzheimer's disease 1.1×10-39 17474819 (PMID) GRASP2 nonQTL
Longevity (90 years and older) 3×10-36 24688116 (PMID) GWAS Catalog via SNiPA
APOB (apolipoprotein B) 3.1×10-32 23100282 (PMID) GRASP2 nonQTL
Metabolic syndrome domains (Atherogenic Dyslipidemia - PC1) 1×10-31 22022282 (PMID) GRASP2 nonQTL
APOE (apolipoprotein E) 8.1×10-31 20442857 (PMID) GRASP2 nonQTL
Lp-PLA2 activity 4.9×10-30 22003152 (PMID) GRASP2 nonQTL
Lipoprotein-associated phospholipase A2 activity and mass 5×10-30 22003152 (PMID) GWAS Catalog via SNiPA
Rate of age-related cognitive decline 3.7×10-27 22054870 (PMID) GRASP2 nonQTL
Cognitive decline 4×10-27 22054870 (PMID) GWAS Catalog via SNiPA
C-reactive protein 5×10-27 19567438 (PMID) GWAS Catalog via SNiPA
Longevity (85 years and older) 2×10-26 24688116 (PMID) GWAS Catalog via SNiPA
HDL cholesterol 2.3×10-22 20686565 (PMID) GRASP2 nonQTL
Lipoprotein-associated phospholipase A2 activity (Lp-PLA2) 9.2×10-21 23118302 (PMID) GRASP2 nonQTL
LDL cholesterol in serum 1.2×10-20 18262040 (PMID) GRASP2 nonQTL
Advanced age-related macular degeneration 2×10-20 23455636 (PMID) GRASP2 nonQTL
Age-related macular degeneration 2×10-20 23455636 (PMID) GWAS Catalog via SNiPA
Total cholesterol (males) 6×10-20 20686565 (PMID) GRASP2 nonQTL
Longevity 2×10-16 21740922 (PMID) GWAS Catalog via SNiPA
Lipid traits 1×10-14 24023261 (PMID) GWAS Catalog via SNiPA
Alzheimer's disease (age of onset) 4.1×10-14 22005931 (PMID) GRASP2 nonQTL
LDL cholesterol response to statins 3.7×10-12 22368281 (PMID) GRASP2 nonQTL
Alzheimer's disease biomarkers 4×10-12 23419831 (PMID) GWAS Catalog via SNiPA
Metabolic syndrome domains (Vascular Inflammation - PC1) 5×10-12 22022282 (PMID) GRASP2 nonQTL
High-sensitivity C-reactive protein (CRP) 7.1×10-11 22291609 (PMID) GRASP2 nonQTL
LDL cholesterol response to statins (first post-treatment LDL cholesterol) 1.2×10-9 22368281 (PMID) GRASP2 nonQTL
Advanced age-related macular degeneration (geographic atrophy) 1.9×10-9 23455636 (PMID) GRASP2 nonQTL
Advanced age-related macular degeneration (choroidal neovascularization) vs. no AMD 2.8×10-8 23455636 (PMID) GRASP2 nonQTL
Serum C-reactive protein 2.9×10-7 21196492 (PMID) GRASP2 nonQTL
Type 2 diabetes 3.2×10-7 22885922 (PMID) Supplemental file
APOB (apolipoprotein B) response after 40mg daily simvastatin treatment 5.7×10-7 23100282 (PMID) GRASP2 nonQTL
LDL cholesterol change with statins 6.3×10-7 20339536 (PMID) GRASP2 nonQTL
Metabolic syndrome domains (Central obesity) 1.2×10-6 22022282 (PMID) GRASP2 nonQTL
Coronary artery disease (CAD) 1.5×10-6 20864672 (PMID) GRASP2 nonQTL
Quantitative traits 2×10-6 19197348 (PMID) GWAS Catalog via SNiPA
Gene expression of CD81 in peripheral blood monocytes 3.4×10-6 20502693 (PMID) GRASP2 eQTL
Gene expression of MAD1L1 in blood 3.5×10-6 21829388 (PMID) GRASP2 eQTL
Waist circumference 3.6×10-6 19557197 (PMID) GRASP2 nonQTL
Waist-to-hip ratio, adjusted for BMI 4.2×10-6 25673412 (PMID) Supplemental file
LDL cholesterol response after 40mg daily simvastatin treatment 6.4×10-6 23100282 (PMID) GRASP2 nonQTL
Waist-to-hip ratio 7.6×10-6 25673412 (PMID) Supplemental file
Gene expression of CCDC86///GPR44 in blood 9.1×10-6 21829388 (PMID) GRASP2 eQTL
Total cholesterol change with statins 1.6×10-5 20339536 (PMID) GRASP2 nonQTL
cg23184690 (chr19:45429795) 4.4×10-5 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Coronary artery disease (CAD), combined control dataset 1.7×10-4 17554300 (PMID) GRASP2 nonQTL
Coronary heart disease (CHD) or coronary artery disease (CAD) 2.1×10-4 22003152 (PMID) GRASP2 nonQTL
Triglycerides (ln) 3×10-4 23063622 (PMID) GRASP2 nonQTL
Fasting glucose 3.1×10-4 22885924 (PMID) Supplemental file
Lp-PLA2 mass 4.3×10-4 22003152 (PMID) GRASP2 nonQTL
Waist circumfence 4.5×10-4 25673412 (PMID) Supplemental file

Trans-association with RUXF supports role of splicing in Alzheimer's disease

This locus is discussed in the main paper.


Boxplot of the ratio between Small Nuclear Ribonucleoprotein F (SNRPF aka RUXF) and Apolipoprotein E (isoform E2) with rs4420638 (Locus 306); Scatterplot of the ratio between SNRPF and APOE-2, coloured by genotype (black = major allele homozygotes, red = heterozygotes, green = minor allele homozygotes; means by genotype = large filled circles); subnetwork showing edges to three identified pQTLs at the APOE locus.

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.