All cases met 1987 American College of Rheumatology diagnostic criteria26 (link), were diagnosed by a board-certified rheumatologist, and were confirmed as anti-CCP positive. Samples came from multiple studies, each receiving approval from the appropriate institutional review boards; all participants signed informed consent.
For primary analysis, we used six sample collections (Supplementary Table 1 ) from the United Kingdom (WTCCC), Sweden (EIRA), Canada (CANADA), United States (NARAC-I and NARAC-III), and Boston (BRASS), from a recent rheumatoid arthritis GWAS meta-analysis13 (link). We followed the quality control steps outlined in the original publication. Additionally, we excluded WTCCC cases that were not confirmed as anti-CCP positive, WTCCC shared controls used to study other phenotypes, and individuals that failed HLA-DRB1 phasing (n=57 individuals). All individuals were self-described white and of European descent. In total, there were 5,018 cases and 14,974 controls.
For secondary analysis, we used a South Korean collection of 616 cases and 675 controls recruited at the Hanyang University Hospital for Rheumatic Diseases in Seoul, described in detail elsewhere18 (link). Our study followed quality control steps outlined in the original publication. We excluded cases not confirmed as anti-CCP positive, and individuals not successfully genotyped for HLA-DRB1 classical alleles.
For all samples, we had access to genome-wide SNP data. The European samples were genotyped on different platforms (Supplementary Table 1 ). South Korean samples were genotyped with Illumina HumanHap-550v3 or 660W platforms. All South Korean samples, a subset of WTCCC samples (n = 700, all controls), and a subset of NARAC-I (n = 450) samples, had full genotype data to 4-digit resolution at the HLA-DRB1 locus. Korean samples were genotyped with polymerase chain reaction sequence-based typing (PCR-SBT); NARAC samples were genotyped with sequence specific oligonucleotide (SSO) genotyping9 (link),19 (link). Some WTCCC controls were part of the 1958 British Birth Cohort27 (link), and were HLA typed at the Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory; that data was made available through the European Genome-phenome Archive (EGA).
For primary analysis, we used six sample collections (
For secondary analysis, we used a South Korean collection of 616 cases and 675 controls recruited at the Hanyang University Hospital for Rheumatic Diseases in Seoul, described in detail elsewhere18 (link). Our study followed quality control steps outlined in the original publication. We excluded cases not confirmed as anti-CCP positive, and individuals not successfully genotyped for HLA-DRB1 classical alleles.
For all samples, we had access to genome-wide SNP data. The European samples were genotyped on different platforms (
