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Genes and Immunity
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Genes and Immunity
Article . 2016 . Peer-reviewed
License: Springer TDM
Data sources: Crossref
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Autoimmune risk variants in ERAP2 are associated with gene-expression levels in thymus

Authors: I S M, Gabrielsen; M K, Viken; S S, Amundsen; H, Helgeland; K, Holm; S T, Flåm; B A, Lie;

Autoimmune risk variants in ERAP2 are associated with gene-expression levels in thymus

Abstract

Genetic polymorphisms in the endoplasmic reticulum aminopeptidase (ERAP)1 and ERAP2 genes have been associated with several autoimmune diseases (AIDs) at a genome-wide significance level. In this study, we performed a cis expression quantitative trait locus (eQTL) screen to investigate whether seven fine-mapped AID single-nucleotide polymorphisms (SNPs) in the ERAP-region influence the gene-expression levels of ERAP1 and ERAP2 in thymus. After quality control, we identified six significant eQTLs. We further assessed the peak eQTL signals, and both genes showed highly significant and independent thymic eQTL signals (P=2.16 × 10-15 and P=8.22 × 10-23, respectively). Interestingly, the peak eQTL signal overlapped with the AID risk loci in ERAP2 (r2>0.94), but were distinct in ERAP1 (r2<0.4). Finally, among the SNPs showing the most significant eQTL associations with ERAP2 (P<3.4 × 10-20), six were located within transcription factor motifs in an enhancer region in thymus. Our study therefore reveals the fine-mapped AID risk variants that act as eQTLs with ERAP2 in thymus, and highlights the potential causal regulatory variants.

Keywords

Male, Quantitative Trait Loci, Gene Expression, Infant, Thymus Gland, Aminopeptidases, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Autoimmune Diseases, Minor Histocompatibility Antigens, Haplotypes, Organ Specificity, Risk Factors, Child, Preschool, Humans, Female, Child

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
9
Top 10%
Average
Average
bronze