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

Genes & Immunity volume 17, pages 406–411 (2016)Cite this article

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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.

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Acknowledgements

We thank Harald Lindberg at Oslo University Hospital for providing the thymus tissues and Hege D Sollid for helping prepare the DNA and RNA samples. The Genomics Core Facility, Oslo University Hospital and University of Oslo, performed the gene-expression analyses. The Ichip genotyping was performed at the Institute of Clinical Molecular Biology Genotyping Platform, Kiel University. We also thank Nimo Hatinoor for performing the Taqman assays. This work was supported by grants from the Research Council of Norway, the Norwegian Diabetes Association, the South-Eastern Norway Regional Health Authorities and Novo Nordisk.

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Authors and Affiliations

  1. Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway

    I S M Gabrielsen, M K Viken, S S Amundsen, H Helgeland, S T Flåm & B A Lie

  2. K. G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway

    I S M Gabrielsen, H Helgeland, S T Flåm & B A Lie

  3. Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway

    M K Viken

  4. Division of Cancer Medicine, Norwegian PSC Research Center, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway

    K Holm

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  1. I S M Gabrielsen
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Correspondence to I S M Gabrielsen.

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Gabrielsen, I., Viken, M., Amundsen, S. et al. Autoimmune risk variants in ERAP2 are associated with gene-expression levels in thymus. Genes Immun 17, 406–411 (2016). https://doi.org/10.1038/gene.2016.39

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