ObjectiveTo examine associations of HLA class I and class II alleles with ankylosing spondylitis (AS) in three cohorts of patients of European, Asian and African ancestry.MethodsHLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1 alleles were genotyped in 1948 unrelated white and 67 African-American patients with AS from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort, the North American Spondylitis Consortium and Australo-Anglo-American Spondyloarthritis Consortium, 990 white and 245 African-American Controls and HLA-B alleles in 442 Han Chinese patients with AS and 346 controls from Shanghai and Gansu, China. In addition to the case:control analyses,HLA-B*27-negative patients with AS were analysed separately, and logistic regression and ‘relative predispositional effects’ (RPE) analyses were carried out to control for the major effect ofHLA-B*27on disease susceptibility.ResultsAlthough numerous associations were seen between HLA alleles and AS in whites, among HLA-B*27-negative patients with AS , positive associations were seen withHLA-A*29, B*38, B*49, B*52, DRB1*11andDPB1*03:01and negative associations withHLA-B*07, HLA-B*57, HLA-DRB1*15:01, HLA-DQB1*02:01andHLA-DQB1*06:02. Additional associations withHLA-B*14andB*40(B60) were observed via RPE analysis, which excludes theHLA-B*27alleles. The increased frequency ofHLA-B*40:01and decreased frequency ofHLA-B*07was also seen in Han Chinese and African-Americans with AS.HLA-B*08was decreased in whites with acute anterior uveitis.ConclusionsThese data, analysing the largest number of patients with AS examined to date in three ethnic groups, confirm that other HLA class I and II alleles other than HLA-B*27 to be operative in AS predisposition.