ERAP1 association with ankylosing spondylitis is attributable to common genotypes rather than rare haplotype combinations

Roberts, Amity
Appleton, Louise
Cortes, Adrian
Vecellio, Matteo
Lau, Jonathan
Watts, Laura
Brown, Matt
Wordsworth, Paul (B.P.)

Publication date

January 2017

DOI

10.1073/pnas.1618856114

Publisher

Proceedings of the National Academy of Sciences

ISSN

0027-8424

Citation count (estimate)

Abstract

Free to read at publisher's site. We investigated the proposal that ankylosing spondylitis (AS) is associated with unusual ERAP1 genotypes. ERAP1 haplotypes were constructed for 213 AS cases and 46 rheumatoid arthritis controls using family data. Haplotypes were generated from five common ERAP1 single nucleotide polymorphisms (SNPs)—rs2287987 (M349V), rs30187 (K528R), rs10050860 (D575N), rs17482078 (R725Q), and rs27044 (Q730E). Haplotype frequencies were compared using Fisher’s exact test. ERAP1 haplotypes imputed from the International Genetics of AS Consortium (IGAS) Immunochip study were also studied. In the family study, we identified only four common ERAP1 haplotypes (“VRNQE,” “MKDRQ,” “MRDRE,” and “MKDRE”) in both AS cases and control...