HelmholtzZentrum munich
WCMC

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

ONLINE SUPPLEMENTARY INFORMATION

Ideogram
Proteome annotation
Locus annotations

Locus 389

Top associations per target

Target cis/​trans Study SNP SNP location Maj/​min allele MAF N βinv seinv Pinv fclog Plog Praw
ASAHL trans Discovery rs2559856 12:102,089,561 G/A 0.44 994 -0.305 0.043 3.6×10-12 -1.140 1.4×10-11 4.5×10-8
ASAHL trans Replication rs2559854 12:102,090,246 G/A 0.49 337 0.264 0.069 1.4×10-4 1.140 1.3×10-4 3×10-4

 

Regional association plots

N-acylethanolamine-hydrolyzing acid amidase (ASAHL)

 

Boxplots and histograms for top associations

N-acylethanolamine-hydrolyzing acid amidase (ASAHL)

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

N-acylethanolamine-hydrolyzing acid amidase (ASAHL)

Target (abbrv.) ASAHL
Target (full name) N-acylethanolamine-hydrolyzing acid amidase
Somalogic ID (Sequence ID) SL008611 (3173-49_2)
Entrez Gene Symbol NAAA
UniProt ID Q02083
UniProt Comment
  • Degrades bioactive fatty acid amides to their corresponding acids, with the following preference: N-palmitoylethanolamine > N-myristoylethanolamine > N-lauroylethanolamine = N-stearoylethanolamine > N-arachidonoylethanolamine > N-oleoylethanolamine. Also exhibits weak hydrolytic activity against the ceramides N-lauroylsphingosine and N-palmitoylsphingosine.

All locus annotations are based on the sentinel SNP (rs2559856) and 40 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
  • CHPT1 choline phosphotransferase 1
  • GNPTAB N-acetylglucosamine-1-phosphate transferase, alpha and beta subunits

 

Results from other genome-wide association studies

Trait P Study Source
Gene expression of CHPT1 in blood 2.3×10-129 21829388 (PMID) GRASP2 eQTL
cg24337881 (chr12:102091411) 4.9×10-54 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Gene expression of CHPT1 in peripheral blood monocytes 2.7×10-33 20502693 (PMID) GRASP2 eQTL
Gene expression of CHPT1 in CEU-CHB-JPT-YRI lymphoblastoid cell lines 8.1×10-22 17873874 (PMID) GRASP2 eQTL
Gene expression of CHPT1 in CD4+ lymphocytes 1.2×10-20 20833654 (PMID) GRASP2 eQTL
Methylation levels at chr12:100615111-100615161 [hg18 coord, probe cg12213457] in Frontal cortex 7.7×10-17 20485568 (PMID) GRASP2 meQTL
Gene expression of CHPT1 [probe 221675_s_at] in lymphoblastoid cell lines 9×10-17 17873877 (PMID) GRASP2 eQTL
Gene expression of CHPT1 (probeID ILMN_1729112) in whole blood 2.2×10-16 22692066 (PMID) GRASP2 eQTL
Methylation levels at chr12:100615111-100615161 [hg18 coord, probe cg12213457] in Temporal cortex 6.8×10-16 20485568 (PMID) GRASP2 meQTL
Gene expression of CHPT1 in lymphoblastoid cell lines 5.3×10-14 17873877 (PMID) GRASP2 eQTL
CHPT1 gene expression 1.1×10-12 21798870 (PMID) GRASP2 eQTL
Methylation levels at chr12:100615111-100615161 [hg18 coord, probe cg12213457] in Caudal pons 8.9×10-12 20485568 (PMID) GRASP2 meQTL
Gene expression of CHPT1 in CHB-JPT lymphoblastoid cell lines 1.1×10-11 17873874 (PMID) GRASP2 eQTL
Gene expression of CHPT1 [probe 230364_at] in lymphoblastoid cell lines 1.3×10-9 17873877 (PMID) GRASP2 eQTL
Gene expression of CHPT1 [probe ILMN_24076] in osteoblasts treated with PGE2 2×10-8 21283786 (PMID) GRASP2 eQTL
Gene expression of CHPT1 [probe 1559739_at] in lymphoblastoid cell lines 3.1×10-8 17873877 (PMID) GRASP2 eQTL
Gene expression of CHPT1 [probe ILMN_24076] in untreated osteoblasts 1.1×10-6 21283786 (PMID) GRASP2 eQTL
Gene expression of CHPT1 in blood cells in Celiac disease 1.1×10-6 19128478 (PMID) GRASP2 eQTL
cg23536555 (chr12:102059908) 7.5×10-6 10.1101/033084 (DOI) BIOS QTL cis-meQTLs
Gene expression of TAGLN2 in peripheral blood monocytes 8.9×10-6 20502693 (PMID) GRASP2 eQTL
Gene expression of CHPT1 in normal prepouch ileum 2.4×10-5 23474282 (PMID) GRASP2 eQTL
Gene expression of CHPT1 [probeset 221675_s_at] in sputum 2.1×10-4 21949713 (PMID) GRASP2 eQTL

Functional match between cis-SNP in Choline Phosphotransferase and trans-association in N-Acylethanolamine Acid Amidase.

This locus harbours a non-replicated trans-pQTL with N-acylethanolamine-hydrolyzing acid amidase (NAAA). The likely causative cis-variant is located in Choline Phosphotransferase 1 (CHPT1). CHPT1 catalyses the phosphatidylcholine biosynthesis from CDP-choline. NAAA degrades bioactive fatty acid amides to their corresponding acids, with the following preference: N-palmitoylethanolamine > N-myristoylethanolamine > N-lauroylethanolamine = N-stearoylethanolamine > N-arachidonoylethanolamine > N-oleoylethanolamine, which links CHPT1 and NAAA by their biochemical activities.

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.