A genome-wide association study meta-analysis in individuals of European and Asian ancestries with 29,880 rheumatoid arthritis cases and 73,758 controls.
Meta-analysis was done in three stages. Stage1 meta-analysis (22 GWAS from 19,234 cases and 61,565 controls of European and Asian ancestry) followed by two-step replication, stage 2 in silico replication (2 GWAS from 3,708 RA cases and 5,535 controls of Europeans and Asians) and stage 3 de novo replication (2 GWAS from 6938 RA cases and 6658 controls of Europeans and Asians). Meta-analysis was performed for the trans-ethnic study (both Europeans and Asians), European study, and Asian study separately.
Approximately 10 million snps were evaluated in this study. Post QC whole-genome imputation was performed using 1000 Genomes Project Phase I data (European and Asian) with Minimac (release 2011-10-27). The combined analysis identified 42 novel RA risk loci, at a genome-wide level of significance (P < 5.0 x 10-8), in any of the trans-ethnic, European or Asian meta-analyses. The study also confirms 59 known RA risk loci, at a suggestive level of association (P < 5.0 x 10-6) from previous studies, increasing the total number of confirmed RA risk loci to 101 (including the MHC region), out of which 5 loci demonstrated population-specific associations.
Whole Genome Association Study
GWAS QC Criteria:
Samples were excluded due to:
- Stage1 : Call rate < 0.95 (European) and < 0.90 (Asian)
- Stage2 : Call rate < 0.95 (European & Asian)
SNPs were excluded due to:
- Stage1: Call rate < 0.95 (European) and < 0.90 (Asian)
- Stage2: Call rate < 0.95 (European & Asian
- Stage1: MAF < 0.01 (European & Asian)
- Stage2: MAF < 0.01 (European) and < 0.05 (Asian)
- Stage1: Deviation from Hardy-Weinberg equilibrium, p < 10-6 (European) and p < 10-7 (Asian)
- Stage2: Deviation from Hardy-Weinberg equilibrium, p < 10-4 (European) and p < 10-3 (Asian)
Imputation QC Criteria:
Excluded imputed SNPs with
- MAF < 0.005 in RA cases and controls
- Low imputation score, Rsq < 0.5 for genome-wide array and < 0.7 for Immunochip for each study.
GDXHsS00035 meets the following criteria:
Study for a Disease