Investigating the genetic association between ERAP1 and ankylosing spondylitis

Harvey, D., Pointon, J. J., Evans, D. M., Karaderi, T., Farrar, C., Appleton, L. H., Sturrock, R. D., Stone, M. A., Oppermann, U., Brown, Matthew A., & Wordsworth, B. P. (2009) Investigating the genetic association between ERAP1 and ankylosing spondylitis. Human Molecular Genetics, 18(21), pp. 4204-4212.

View at publisher (open access)


A strong association between ERAP1 and ankylosing spondylitis (AS) was recently identified by the Wellcome Trust Case Control Consortium and the Australo-Anglo-American Spondylitis Consortium (WTCCC-TASC) study. ERAP1 is highly polymorphic with strong linkage disequilibrium evident across the gene. We therefore conducted a series of experiments to try to identify the primary genetic association(s) with ERAP1. We replicated the original associations in an independent set of 730 patients and 1021 controls, resequenced ERAP1 to define the full extent of coding polymorphisms and tested all variants in additional association studies. The genetic association with ERAP1 was independently confirmed; the strongest association was with rs30187 in the replication set (P = 3.4 × 103). When the data were combined with the original WTCCC-TASC study the strongest association was with rs27044 (P = 1.1 × 10-9). We identified 33 sequence polymorphisms in ERAP1, including three novel and eight known non-synonymous polymorphisms. We report several new associations between AS and polymorphisms distributed across ERAP1 from the extended case-control study, the most significant of which was with rs27434 (P = 4.7 × 10-7). Regression analysis failed to identify a primary association clearly; we therefore used data from HapMap to impute genotypes for an additional 205 non-coding SNPs located within and adjacent to ERAP1. A number of highly significant associations (P < 5 × 10-9) were identified in regulatory sequences which are good candidates for causing susceptibility to AS, possibly by regulating ERAP1 expression. © 2009 The Author(s).

Impact and interest:

71 citations in Scopus
Search Google Scholar™
73 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 89409
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By :58
Export Date: 21 September 2015
Correspondence Address: Wordsworth, B.P.; Botnar Research Centre, University of Oxford, Institute of Musculoskeletal Science, Windmill Road, Headington, Oxford OX3 7LD, United Kingdom; email:
Keywords: aminopeptidase, endoplasmic reticulum associated aminopeptidase 1, unclassified drug, ankylosing spondylitis, article, controlled study, gene location, gene sequence, genetic association, genetic identification, genetic variability, genotype, human, major clinical study, priority journal, protein expression, protein function, protein structure, regulatory sequence, single nucleotide polymorphism, Aminopeptidases, Case-Control Studies, Cohort Studies, Gene Frequency, Genetic Predisposition to Disease, Humans, Linkage Disequilibrium, Logistic Models, Models, Molecular, Polymorphism, Single Nucleotide, Protein Conformation, Protein Structure, Tertiary, Sequence Analysis, DNA, Spondylitis, Ankylosing
DOI: 10.1093/hmg/ddp371
ISSN: 0964-6906
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2009 The Authors
Deposited On: 23 Oct 2015 00:19
Last Modified: 22 Aug 2016 23:10

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page