ArticleAmerican journal of human genetics2023
Variation in ERAP2 has opposing effects on severe respiratory infection and autoimmune disease.
Article in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Estimating in silico causal effects of DNA methylation on gene expression through genetic anchors in airway epithelium in asthma.Science advances · 2026Article
- Restoring balance in atopic disorders: insights into type 2 immunity and chronic inflammation.Frontiers in immunology · 2026Review
- Cell type-specific eQTL analysis of COVID-19 based on single-cell transcriptomic data.NAR genomics and bioinformatics · 2025Article
- Association of Chromosome 3p21.32 Haplotype Blocks Introgressed from Neanderthals with Critical COVID-19 in a Spanish Cohort.Life (Basel, Switzerland) · 2025Article
- Genetic determinants of monocyte splicing are enriched for disease susceptibility loci.Nature communications · 2025Article
- Evaluating the causal effect of circulating proteome on the risk of Juvenile idiopathic arthritis: an omics pipeline study.Pediatric rheumatology online journal · 2025Article
- Population-scale sequencing resolves correlates and determinants of latent Epstein-Barr Virus infection.bioRxiv : the preprint server for biology · 2025Article
- Article
- Unveiling the impact of ERAP1 and ERAP2 on migration, angiogenesis and ER stress response.Frontiers in cell and developmental biology · 2025Review
- Transcriptome-wide Mendelian randomization during CD4Nature communications · 2024Article
- The effect of rs2910686 on ERAP2 expression in IBD and epithelial inflammatory response.Journal of translational medicine · 2024Article
- Transcriptome-wide association studies associated with Crohn's disease: challenges and perspectives.Cell & bioscience · 2024Review
- Article
- A cis-regulatory element regulates ERAP2 expression through autoimmune disease risk SNPs.Cell genomics · 2024Article
- Association ofFrontiers in immunology · 2024Article
- Evaluating the causal effect of circulating proteome on the risk of inflammatory bowel disease-related traits using Mendelian randomization.Frontiers in immunology · 2024Article
- Evolutionary immuno-genetics of endoplasmic reticulum aminopeptidase II (ERAP2).Genes and immunity · 2023Review
- Reply to Barton et al: signatures of natural selection during the Black Death.bioRxiv : the preprint server for biology · 2023Article
- Tracking of activated cTfh cells following sequential influenza vaccinations reveals transcriptional profile of clonotypes driving a vaccine-induced immune response.Frontiers in immunology · 2023Article
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
ERAP2 is an aminopeptidase involved in immunological antigen presentation. Genotype data in human samples from before and after the Black Death, an epidemic due to Yersinia pestis, have marked changes in allele frequency of the single-nucleotide polymorphism (SNP) rs2549794, with the T allele suggested to be deleterious during this period, while ERAP2 is also implicated in autoimmune diseases. This study explored the association between variation at ERAP2 and (1) infection, (2) autoimmune disease, and (3) parental longevity. Genome-wide association studies (GWASs) of these outcomes were identified in contemporary cohorts (UK Biobank, FinnGen, and GenOMICC). Effect estimates were extracted for rs2549794 and rs2248374, a haplotype tagging SNP. Additionally, cis expression and protein quantitative trait loci (QTLs) for ERAP2 were used in Mendelian randomization (MR) analyses. Consistent with decreased survival in the Black Death, the T allele of rs2549794 showed evidence of association with respiratory infection (odds ratio; OR for pneumonia 1.03; 95% CI 1.01-1.05). Effect estimates were larger for more severe phenotypes (OR for critical care admission with pneumonia 1.08; 95% CI 1.02-1.14). In contrast, opposing effects were identified for Crohn disease (OR 0.86; 95% CI 0.82-0.90). This allele was shown to associate with decreased ERAP2 expression and protein levels, independent of haplotype. MR analyses suggest that ERAP2 expression may be mediating disease associations. Decreased ERAP2 expression is associated with severe respiratory infection with an opposing association with autoimmune diseases. These data support the hypothesis of balancing selection at this locus driven by autoimmune and infectious disease.
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Registered trials
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